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At least 217 records · Page 12Linked to original sources
PubMed1989

Defective repair of UV-damaged DNA in human tumor and SV40-transformed human cells but not in adenovirus-transformed human cells.

The DNA repair capacities of five human tumor cell lines, one SV40-transformed human cell line and one adenovirus-transformed human cell line were compared with that of normal human fibroblasts using a sensitive host cell reactivation (HCR) technique. Unirradiated and UV-irradiated suspensions of adenovirus type 2 (Ad 2) were assayed for their ability to form viral structural antigens (Vag) in the various cell types using immunofluorescent staining. The survival of Vag formation for UV-irradiated Ad 2 was significantly reduced in all the human tumor cell lines and the SV40-transformed human line compared to the normal human fibroblasts, but was apparently normal in the adenovirus-transformed human cells. D0 values for the UV survival of Ad 2 Vag synthesis in the tumor and virally transformed lines expressed as a percentage of that obtained on normal fibroblast strains were used as a measure of DNA repair capacity. Percent HCR values ranged from 26 to 53% in the tumor cells. These results indicate a deficiency in the repair of UV-induced DNA damage associated with human tumorigenesis and the transformation of human cells by SV40 but not the transformation of human cells by adenovirus.

Adenoviruses, Human↗
PubMed1983

Plasmid transformation in Agmenellum quadruplicatum PR-6: construction of biphasic plasmids and characterization of their transformation properties.

Biphasic, chimeric plasmids for the transformation of Agmenellum quadruplicatum PR-6 (Synechococcus sp. strain 7002) were constructed by splicing the 3.0-megadalton cryptic plasmid from strain PR-6 into plasmids pBR322 and pBR325 from Escherichia coli. Transformants of either E. coli or strain PR-6 by these plasmids could be detected on the basis of the drug resistance marker(s) carried by the chimeric plasmids. Plasmid DNA isolated from a PR-6 transformant transformed PR-6 much more efficiently than plasmid DNA prepared from E. coli. Plasmids from which the AvaI recognition site was deleted (AvaI is an isoschizomer of the AquI restriction endonuclease of strain PR-6) also transformed strain PR-6 much more efficiently than did plasmids containing the AvaI recognition site. These and other results suggest that AquI strongly effects plasmid transformation when the donor plasmid contains an unmodified AquI recognition site. Multimeric forms of the chimeric plasmids are also much more efficient at transforming strain PR-6 than are the analogous monomeric forms.

Chimera↗
PubMed1991

Molecular cloning of two linked loci that increase the transformability of transformation-deficient mutants of Haemophilus influenzae.

A plasmid containing a 13.3-kb insert (pER194) was isolated from an EcoRI genomic library of Haemophilus influenzae on the basis of its ability to increase the transformability of the transformation-deficient mutants Com-78 and Com-101. The plasmid failed to increase the transformability of the Rec-1 and Rec-2 mutants, indicating that the mutations producing the Com-78 and Com-101 phenotypes are distinct from those giving rise to the Rec-1 and Rec-2 phenotypes. The physical mapping of the cloned fragment on the H. influenzae chromosome was found to be consistent with the genetic mapping of the Com-101 trait. A 2.8-kb EcoRI-BglII subfragment, representing one end of the 13.3-kb clone, was found to increase the transformation frequency of the Com-78 and Com-101 mutants when supplied in trans, indicating that the subfragment carries one or more loci required for chromosomal transformation. The corresponding region of the Com-101 chromosome was determined by hybridization analysis to contain a 0.3-kb insertion, suggesting that the Com-101 strain may contain an insertion mutation at this locus. A 3.0-kb EcoRI-MluI subfragment, representing the other end of the 13.3-kb EcoRI fragment, was found to increase the transformation frequency of the Com-101 mutant but not of the Com-78 mutant, suggesting that the Com-101 phenotype results from a complex genotype involving mutations at two or more transformation-related loci. This conclusion is consistent with data indicating that the Com-101 trait can be genetically separated into at least two components.

Chromosome Mapping↗
PubMed1982

Deletions within the transformation-specific RNA sequences of acute leukemia virus MC29 give rise to partially transformation-defective mutants.

The viral RNAs of three nonconditional mutants of avian myelocytomatosis virus MC29 were analyzed. These mutants, which were originally isolated from the quail producer line Q10 and were designated 10A, 10C, and 10H, have lost most of the ability to transform hematopoietic cells in vitro and to induce tumors in vivo, but they still transform cultured fibroblasts with the same efficiency as wild-type (wt) MC29. Electrophoretic analyses showed that the mutant genomic RNAs were smaller than the 5.7-kilobase genome of wt MC29; the genomes of mutants 10A, 10C, and 10H were about 5.5, 5.3, and 5.1 kilobases long, respectively. Analyses of the transformation-specific sequences of these mutant RNAs by a combination of T(1) oligonucleotide fingerprinting and hybridization with cDNA from the transformation-specific sequences myc of wt MC29 or competition hybridization including wt MC29 RNA revealed that deletions of myc-specific sequences had occurred. The deletions in all three mutants overlapped, since they all had lost one particular myc-specific oligonucleotide. In agreement with the size of the genomic RNAs, mutants 10C and 10H had lost two additional myc oligonucleotides, and mutant 10A contained a modified myc oligonucleotide. The locations of the deletions were deduced from comparisons with previously established oligonucleotide maps of several members of the MC29 subgroup of acute leukemia viruses and by hybridization of wt and mutant RNAs to molecularly cloned subgenomic fragments of wt MC29 proviral DNA, representing the 5' and 3' domains of the myc sequence. We found that the deleted sequences represented overlapping internal segments of the myc sequence and that the borders of myc with the partial complements of the virion genes gag and env appeared to be conserved in mutant and wt MC29 RNAs. The correlation between the altered transforming potential for hematopoietic cells and the partial deletion of myc in the mutant RNAs provided direct genetic evidence for the involvement of myc in oncogenesis. However, the unaffected efficiency of these mutants in fibroblast transformation suggested that the deleted sequences are not essential for the fibroblast-transforming potential of the onc gene of MC29.

Animals↗
PubMed1984

Action of temperature-sensitive mutants of myeloproliferative sarcoma virus suggests that fibroblast-transforming and hematopoietic transforming viral properties are related.

The myeloproliferative sarcoma virus is molecularly related to the Moloney sarcoma virus (Pragnell et al., J. Virol. 38:952-957, 1981), but causes both fibroblast transformation in vitro and leukemic changes--including spleen focus formation--in adult mice. The fibroblast transforming properties of myeloproliferative sarcoma virus were used to select viral temperature-sensitive mutants at 39.5 degrees C, the nonpermissive temperature. These mutants are temperature sensitive in the maintenance of the transformed state. This was also shown by cytoskeletal changes of the infected cells at permissive and nonpermissive temperatures. Viruses released from cells maintained at both the permissive and nonpermissive temperature are temperature sensitive in fibroblast transformation functions. All temperature-sensitive mutants show only a low reversion rate to wild-type transforming function. The myeloproliferative sarcoma virus temperature-sensitive mutants are inefficient in causing leukemic transformation (spleen enlargement, focus formation) in mice at the normal temperature. A method to maintain a low body temperature (33 to 34 degrees C) in mice is described. One temperature-sensitive mutant was checked at low body temperature and did not induce leukemia. These data thus indicate that the same or related viral functions are responsible for hematopoietic and fibroblast transformation.

Animals↗
PubMed1984

Transformation of Neurospora crassa with recombinant plasmids containing the cloned glutamate dehydrogenase (am) gene: evidence for autonomous replication of the transforming plasmid.

We have characterized Neurospora crassa transformants obtained with plasmid pJR2, which consists of the Neurospora glutamate dehydrogenase (am) gene cloned in pUC8 and an am132 host strain which contains a deletion encompassing the cloned fragment. Every one of 33 transformants tested showed extreme meiotic instability: less than 1 or 2% am+ progeny were obtained in initial or successive backcrosses between am+ transformants and am132 or in intercrosses between am+ progeny. Furthermore, am+ progeny from backcrosses gave a high proportion of auxotrophic (am) mitotic segregants during vegetative growth. These results indicate that the am+ character is not stably integrated into chromosomal DNA in any of the transformants tested. Nuclear DNAs from six transformants were analyzed by Southern hybridization. All six transformants contained sequences homologous to pJR2. Four showed restriction fragments expected for unmodified pJR2, but most showed additional bands. Southern blots of undigested DNAs showed that the plasmid sequences are present predominantly in high-molecular-weight form (larger than 20 kilobases). Southern blots showed that auxotrophic (am) progeny from a backcross to am132 had lost restriction bands corresponding to free plasmid but retained additional bands, apparently integrated into chromosomal DNA in a nonfunctional manner. Considered together, these results are most reasonably interpreted as follows: recombinant plasmids containing the am+ gene can replicate autonomously in N. crassa, the free plasmids are present in oligomeric or modified form or both, and plasmid sequences also integrate at multiple sites in the deletion host but in a nonfunctional manner. An alternate interpretation--that tandem repeats of the plasmid are integrated into chromosomal DNA but eliminated during meiosis--cannot be completely excluded. However, stable integration of the am gene can be obtained under a variety of other conditions, viz., using the am gene cloned in a phage lambda vector (J. A. Kinsey and J. A. Rambosek, Mol. Cell. Biol. 4:117-122, 1984), using derivatives of pJR2, or using pJR2 to transform a frameshift mutant.

DNA Replication↗
PubMed1985

Differential transformation of C3H10T1/2 cells by v-mos: sequential expression of transformation parameters.

Extremely small quantities of the product of the transforming gene v-mos of Moloney murine sarcoma virus are able to efficiently transform cells. Recent data indicate the existence of a threshold level for v-mos transformation of NIH3T3 cells. Using mouse mammary tumor virus long terminal repeat sequences or hybrid promoters consisting of mouse mammary tumor virus and Moloney murine sarcoma virus long terminal repeat elements to express v-mos in C3H10T1/2 cells, we established cell lines representing different stages of morphological transformation in vitro. The threshold level for v-mos transformation was considerably lower than that for NIH3T3 cells, because no treatment with dexamethasone or primary selection other than transformation was necessary during standard transfection procedures. Using the cell lines mentioned we established an association of the level of v-mos expression with the transformation parameters examined, but not with p53 levels. Furthermore, the characterization of the different promoters showed (i) that the distal binding site confers hormone responsiveness to Moloney murine sarcoma virus promoter elements and (ii) that artifactual transcription initiation sites can be detected in mouse mammary tumor virus-Moloney murine sarcoma virus hybrid promoters which are, however, not regulated by the hormone.

Animals↗
PubMed1993

Transformation of BALB/c-3T3 cells: I. Investigation of experimental parameters that influence detection of spontaneous transformation.

The frequency of spontaneous morphological transformation is an important variable in measuring chemical-induced transformation in BALB/c-3T3 clone A-31-1-13 cell cultures. Data from 110 experiments, which included benzo[a]pyrene control groups and other chemical treatment groups, were analyzed for factors that influenced spontaneous transformation. Spontaneous transformants demonstrated a continuum of morphological variants (type I, II, and III foci) that fit a normal distribution if converted to log10. The magnitude of transformation depended on the ampule of cryopreserved cells and the serum lot. Although the average frequency was approximately 0.71 x 10(-6) (type III foci/cell that survived and proliferated to confluence), the absolute number of foci/vessel increased in proportion to the surface area of the culture vessel. Thus, the frequency of spontaneous transformation was directly related to the cumulative number of mitoses that occurred in forming the contact-inhibited monolayer. These data are consistent with a hypothesis that spontaneous transformation in BALB/c-3T3 cells is a mutational event or some other single-step phenomenon.

3T3 Cells↗
PubMed1993

Transformation of BALB/c-3T3 cells: V. Transformation responses of 168 chemicals compared with mutagenicity in Salmonella and carcinogenicity in rodent bioassays.

This report describes the activities of 168 chemicals tested in a standard transformation assay using A-31-1-13 BALB/c-3T3 cells. The data set includes 84 carcinogens, 77 noncarcinogens, and 7 research chemicals. Carcinogens included 49 mutagens and 35 nonmutagens; noncarcinogens included 24 mutagens and 53 nonmutagens. The transformation assay did not use an exogenous activation system, thus, all chemical responses depended on the inherent target cell metabolic capacity where metabolic activation was required. The upper dose limit was 100 milli-osmolar because the assay could not discriminate active and inactive chemicals tested above this concentration. Certain physicochemical properties resulted in technical problems that affected chemical biological activity. For example, chemicals that reacted with plastic were usually nonmutagenic carcinogens. Similarly, chemicals that were insoluble in medium, or bound metals, were usually nonmutagenic and nontransforming. Multifactorial data analyses revealed that the transformation assay discriminated between nonmutagenic carcinogens and noncarcinogens; it detected 64% of the carcinogens and only 26% of the noncarcinogens. In contrast, the transformation assay detected most mutagenic chemicals, including 94% of the mutagenic carcinogens and 70% of the mutagenic noncarcinogens. Thus, transformation or Salmonella typuimurium mutagenicity assays could not discriminate mutagenic carcinogens from mutagenic noncarcinogens. Data analyses also revealed that mutagenic chemicals were more cytotoxic than nonmutagenic chemicals; 88% of the mutagens had an LD50 < 5 mM, whereas half of the nonmutagens had an LD50 > 5 mM. Binary data analyses of the same data set revealed that the transformation assay and rodent bioassay had a concordance of 71%, a sensitivity for carcinogens of 80.0%, and a specificity for detecting noncarcinogens of 60%. In contrast, Salmonella mutagenicity assays and rodent bioassays had a concordance of 63%, a sensitivity of 58%, and a specificity of 69%. The transformation assay complemented the Salmonella mutagenesis assay in the identification of nonmutagenic carcinogens; thus, the two assays had a combined 83% sensitivity for all carcinogens and a 75% specificity for nonmutagenic noncarcinogens.

3T3 Cells↗
PubMed2000

Malachite green induced malignant transformation of Syrian hamster embryo (SHE) cells in primary culture: transformation is associated with enhanced expression of altered p53, bcl-2 and decreased sensitivity to apoptosis.

Malachite green (MG) consisting of green crystals with a metallic lustre, is highly soluble in water, cytotoxic to various mammalian cells and also acts as a liver tumor promoter. In view of its industrial importance and possible exposure to human beings, MG poses a potential environmental health hazard. We have previously reported the malignant transformation of Syrian hamster embryo (SHE) cells by MG. In this study, we have made an attempt to study the effects of MG on the induction of apoptosis in normal and MG transformed Syrian hamster embryo cells and the expression of altered p53 and bcl-2 immunohistochemically. Induction of apoptosis was detected by flow cytometry on the basis of G0/G1 hypodiploid peak, Tunel assay and DNA ladder pattern. Flow cytometric analysis showed a dose and time dependent induction of apoptosis by MG in control cells whereas induction of apoptosis by MG was marginal in transformed cells. Tunel assay and DNA ladder pattern also showed decreased apoptosis in transformed cells by MG compared to controls. Immunostaining studies showed intense staining for p53 in transformed cells whereas no staining was observed in control cells. Also transformed cells showed overexpression of bcl-2 with exclusive nuclear localization compared to controls which did not show staining. The present study indicated that MG transformed Syrian hamster embryo cells have decreased sensitivity to apoptosis compared to normal cells and overexpression of altered p53 and bcl-2 seems to be conferring resistance to MG induced apoptosis.

Animals↗
PubMed1977

Continued presence of similar transformation-associated antigens related to murine oncornavirus proteins in -ransformed cells, morphological revertants, and cells restricted in the expression of transformation.

The possible alteration of transformation-related antigens in cells that revert to a normal phenotype but that continue to retain the viral genome, has been investigated in [3H]glucosamine-labeled extracts of rat cells exhibiting a reversible temperature-dependent restriction in the expression of transformation and in a comparison of a morphologically altered mouse cell transformed by the Kirsten sarcoma virus with a flat revertant mouse cell derived from the morphologically transformed cells. With the use of normal goat serum in the presence of dibutyryl cyclic 3':5'-adenosine monophosphate, some differences became obvious in the rat cells restricted in the expression of transformation. However, use of specific antiserum to murine leukemia virus revealed in every case the presence of major components that exhibited an electrophoretic mobility corresponding to about 100,000 daltons both in the parent and revertant mouse cells and in the rat cells exhibiting either untransformed or transformed growth properties. The glycoprotein components detected only by the immune serum may represent a cellular macromolecule antigenically related to an interspecies C-type viral species whose concentration is increased in transformed cells.

Antigens, Neoplasm↗
PubMed1986

Efficient transformation and frequent single-site, single-copy insertion of DNA can be obtained in mouse erythroleukemia cells transformed by electroporation.

Electroporation has recently been shown to have advantages over the commonly used method of calcium phosphate precipitation for obtaining DNA-mediated transformation of certain types of cells. Although mouse erythroleukemia cells and other cells of hematopoietic origin are not transformed at useful frequencies by calcium phosphate-DNA precipitation methods, we obtained high frequencies of transformation (approximately 10(-5)) of these cells with electroporation. Even higher transformation frequencies (approximately 10(-3)) were obtained with human fibroblasts. Another advantage of electroporation was found when analysis of Southern blots of DNA from 243 transformed erythroleukemia cell colonies indicated that, under appropriate conditions, about 79% of the transformed cells had the exogenous DNA integrated in single copies at single sites. Under conditions of higher DNA and lower cell concentrations using fibroblasts, cotransformation was obtained with two plasmids that confer HAT or G418 resistance when integrated into cellular DNA. About 23% of the transformed cells developed both types of resistance. We describe a simple, inexpensive apparatus for carrying out electroporation.

Animals↗
PubMed1983

[Isolation of new transforming viruses from "phenotypically transformed" Sirc cells in a medium with a low concentration of serum or calcium ions].

Possibility of rapid generation of highly transforming viruses from rabbit epithelial corneal cells (Sirc) on the basis of SSAV virus is discussed. The results of the study suggested a relationship between the phenomenon of "phenotypic transformation" with expression of cellular genes and a potential transforming activity. Sirc/SSAV phenotypic transformation was induced by cultivating of cells in a medium with low levels of serum or calcium ions. Subsequent infection of mink lung fibroblasts resulted in generation of 2 new transforming SSAV isolates which induced transformation in cellular lines permissive for SSAV replication. The foci of transformation were of various morphological patterns.

Animals↗
PubMed1984

Surface topography and extent of invasiveness of SV40 virus-transformed hamster brain cells and transformed cell-produced tumors.

Scanning electron microscopy (SEM) was used to study the surface configuration of SV40 virus-transformed 1 day old Syrian hamster brain cells and transformed cell-produced tumors and the alterations in cell membrane configuration that become evident with the development of invasiveness. Cell cultures of dissociated cerebral cortex, brain-stem, cerebellar vermis and cerebellar hemisphere were transformed to a neoplastic state with SV40 virus. The transformed cells were then inoculated intracerebrally into hamsters to produce intracranial tumors, and cell cultures were obtained from these tumors. Invasiveness was determined by reinoculating the transformed or tumor cells intracerebrally into hamsters and examining histological sections of the resulting tumors. Cultures of the transformed and tumor cells were also critical point dried and studied with SEM. Tumors of cerebral cortex and brainstem derivation (Group I) had the histological appearance of astrocytomas and were invasive for adjacent normal brain. With SEM, they were flat, epithelioid, and surrounded by ruffles and microvilli. They grew only in monolayers and showed few of the rounded forms with blebs and/or microvilli typical of mitosis. Tumors of cerebellar vermis and cerebellar hemisphere derivation (Group II) had the histological appearance of primitive neuroectodermal tumors and were not invasive. With SEM, they were more rounded, fusiform or stellate, and lacked surface specializations at their borders. They exhibited multilayered growth and the rounded forms associated with mitosis. Tumor cells of both groups had more surface activity than transformed cells. These observations give some support to the concept that a decrease in contact inhibition of locomotion and an increase in density-dependent inhibition of locomotion and in mobilization are essential for the development of invasiveness in tumors.

Animals↗
PubMed1982

Cells transformed by RNA and DNA tumor viruses produce transforming factors.

The RNA tumor viruses, Kirsten murine sarcoma virus (KiMSV) and Abelson murine leukemia virus, are shown to produce transforming factors (TFs) similar to sarcoma growth factor (SGF) produced by Moloney murine sarcoma virus-transformed 3T3 cells. TF production by KiMSV-transformed cells is dependent on the presence of a functional viral genome. TFs from KiMSV-transformed cells induce the transformed phenotype in normal cells, which suggests that the TFs play a integral role in transformation. We have extended TF production to DNA tumor viruses by demonstrating that cells transformed by simian virus 40 (SV40) and polyoma virus produce a growth factor or factors that render Rat-1 cells anchorage independent. The SV40-induced TF is not related to the KiMSV-induced TF. Last we demonstrate that cells vary in their sensitivity to TFs and propose that tumor cells have an increased responsiveness to TF-induced anchorage-independent growth.

Cell Transformation, Viral↗
PubMed1998

Myofibroblast transformation of cat corneal endothelium by transforming growth factor-beta1, -beta2, and -beta3.

PURPOSE: Under certain pathophysiologic conditions, the corneal endothelium can produce an abnormal posterior collagenous layer (PCL) that reduces light transmission. Previous studies suggest that formation of PCLs can result from transformation of endothelial cells to a proliferative myofibroblast phenotype. The purpose of this study was to determine the potential role of transforming growth factor (TGF)-beta on corneal endothelial transformation. METHODS: Three corneal buttons (6-mm diameter) were obtained from each cornea of 28 adult cats. After a 2-mm diameter mechanical scrape injury was made, each button was cultured for 24, 48, or 72 hours in serum-free medium (SFM) or SFM supplemented with 10% fetal calf serum, TGF-gamma1, TGF-beta2, TGF-beta3, basic fibroblast growth factor (bFGF), or TGF-beta1 and bFGF. Buttons were single and double labeled using phalloidin and antibodies to ZO-1, Ki67, fibronectin, alpha-smooth muscle (SM) actin, and vinculin. Counts of Ki67-positive cells were used as a measure of endothelial proliferation. RESULTS: Organ culture in TGF-beta1, beta2, or beta3 induced myofibroblast transformation of corneal endothelial cells, with formation of stress fibers containing alpha-SM actin, loss of normal pericellular ZO-1 organization, development of extracellular fibronectin fibrils, and formation of focal contacts as indicated by punctate vinculin staining. However, TGF-beta3 did not stimulate endothelial proliferation above that in serum-free control samples. Serum and bFGF each stimulated proliferation significantly, without inducing myofibroblast transformation. A combination of TGF-beta1 and bFGF resulted in both myofibroblast transformation and increased proliferation. CONCLUSIONS: These results suggest that TGF-beta plays a key role in the loss of normal endothelial differentiation, abnormal extracellular matrix synthesis, and myofibroblast transformation, which can induce development of PCLs. However, other factors such as bFGF seem to be required to stimulate concomitant proliferation of corneal endothelium.

Animals↗
PubMed1995

Catechol interferes with TGF-beta-induced elimination of transformed cells by normal cells: implications for the survival of transformed cells during carcinogenesis.

We have recently shown that TGF-beta-treated normal fibroblasts are able to induce apoptosis of transformed fibroblasts, leading to their elimination. Here we describe a test system that allows the quantitative analysis of the elimination of G418-resistant transformed cells by TGF-beta-treated normal cells. This assay system was used to screen for substances that interfere with the elimination of transformed cells. Catechol and hydroquinone, but not resorcinol, were found to represent potent antagonists of TGF-beta-induced elimination of transformed cells by normal cells. Protection of transformed cells from negative effects derived from their cellular environment defines a hitherto unrecognized crucial mechanism for the survival of transformed cells. The protective effect of catechol as seen in this experimental system may act in concert with its co-carcinogenic and promoting activities during carcinogenesis.

Animals↗
PubMed1994

Overexpression of c-K-ras, c-N-ras and transforming growth factor beta co-segregate with tumorigenicity in morphologically transformed C3H 10T1/2 cell lines.

Morphologic transformation and tumorigenicity are separate cellular phenotypes in transformed 10T1/2 cells. We have investigated the levels of expression of genes for c-myc, c-H-ras, c-K-ras, c-N-ras, TGF beta and Rb in 42 morphologically transformed 10T1/2 cell lines, in an attempt to define the molecular mechanisms governing morphologic transformation and tumorigenicity in the 10T1/2 cell system. The 10T1/2 cell lines investigated generally overexpressed mRNAs for c-myc, c-H-ras, and TGF beta relative to the levels expressed by wild-type 10T1/2 cells (levels of expression > 1.5-fold that of wild-type 10T1/2 cells). In contrast, only half of these cell lines overexpressed mRNAs for c-N-ras and/or Rb relative to wild-type 10T1/2 cells, and only 25% overexpressed c-K-ras mRNA. The mean levels of mRNA expression for each of c-K-ras, c-N-ras and TGF beta genes in tumorigenic cell lines were significantly greater than the mean levels of expression in non-tumorigenic cell lines, suggesting an association between tumorigenicity and the levels of expression of these specific genes. In contrast, levels of expression for c-myc, c-H-ras and Rb genes were not correlated with tumorigenicity. Cell lines that coexpressed high levels of c-K-ras, c-N-ras and TGF beta genes were likely to be tumorigenic (11/12 cell lines were tumorigenic), whereas cell lines that coexpressed low levels of these genes were unlikely to be tumorigenic (1/10 cell lines were tumorigenic). High expression of TGF beta was sufficient for tumorigenicity in the absence of high levels of expression of c-K-ras and c-N-ras (5/5 cell lines were tumorigenic). Elevated expression of either c-K-ras or c-N-ras alone was insufficient for tumorigenicity, however, coordinate overexpression of both c-K-ras and c-N-ras was associated with tumorigenicity irrespective of the expression status for TGF beta (13/15 cell lines were tumorigenic). These results suggest that overexpression of c-myc, c-H-ras and TGF beta are commonly associated with, and possibly mechanistically related to, the process of morphologic transformation in 10T1/2 cells. In addition, these results suggest that progression from morphologic transformation to tumorigenicity in 10T1/2 cell lines is frequently accompanied by overexpression of c-K-ras and c-N-ras, and by enhancement of the level of overexpression of TGF beta.

Animals↗