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Biomedical subjects

D Medina

Publications and source records attributed to D Medina.

At least 127 records · Page 7Linked to original sources
PubMed1988

Serine and methionine enhancement of selenite inhibition of DNA synthesis in a mouse mammary epithelial cell line.

Methionine and serine in combination enhanced the inhibitory effect of selenite on cell growth and DNA synthesis of the MOD mammary epithelial cell line. These amino acids also increased the levels of a 58-kd selenoprotein which has been correlated with selenite's effects in previous studies. The use of the amino acids accelerated the onset of inhibition of DNA synthesis by selenite and increased the rate of actual selenoprotein synthesis. The mechanism of enhancement of selenite's effects was possibly due to the amino acids increasing the levels of essential precursors (i.e. seryltRNA(UGA), HSe-) needed for selenoprotein synthesis.

Animals↗
PubMed1988

A morphologically distinct candidate for an epithelial stem cell in mouse mammary gland.

Transplantation studies demonstrate that an epithelial stem cell component must exist in the mouse mammary gland throughout life. Samples taken from any portion of the mammary gland at any age and at any developmental stage, including full functional differentiation, give rise to mammary epithelial outgrowths with complete developmental capacity. Cytological examination of mouse mammary gland explants revealed the presence of morphologically distinct cells distributed sporadically among the mammary epithelium, whose behaviour in vivo and in vitro suggested that they might represent a latent epithelial stem cell population. These pale-staining cells possessed large spherical nuclei, a clear cytoplasm and a round smooth-contoured shape. Electron microscopy confirmed their pale-staining characteristics and revealed a cytoplasm sparsely populated with organellar structures, such as mitochondria and endoplasmic reticulum. Their epithelial genealogy was demonstrated by the presence of terminal bars and tight junctions formed with their epithelial cell neighbours. In vivo, these cells were found among mammary epithelial cell populations in 16-day-old embryos onward in both ductal or lobular structures during all stages of pregnancy, lactation and involution. In explant cultures, these cells did not undertake a secretory morphology in the presence of lactogenic hormones, although occasionally they became immunologically positive for casein. They did not incorporate [3H]-thymidine into their nuclei under any of the experimental conditions used; however, they appeared to undergo mitosis within 4 h regardless of the presence or absence of hormone(s). At 24 h increased numbers of pale cells were found in pairs or in groups. At 72 h in the presence of IFPrl (medium containing insulin, hydrocortisone and prolactin), the pairs and groups of pale cells observed at 24 h were not found. Instead, individual pale cells were seen among groups of cytologically and functionally differentiated secretory epithelial cells. When lactogenic hormones were not present, groups of pale cells were still present in the explants at 72 h. These findings suggest that the pale cells are arrested at G2 phase of the cell cycle and that they give rise by mitosis to daughter cells capable of differentiating in the presence of lactogenic stimuli. Inhibition of DNA synthesis in the explants did not alter these cellular events.

Animals↗
PubMed1987

Characterization of the DIM series of BALB/c preneoplasms for mouse mammary tumor virus-mediated oncogenesis.

The DIM series of preneoplasms, developed from the BALB/c mammary cell line COMMA-D, and DIM-derived tumors were examined for evidence of mouse mammary tumor virus (MMTV) involvement in the tumorigenic process. DIM tissues were shown to be free of exogenous MMTV inasmuch as Southern blot analysis of DNAs extracted from DIM preneoplasms and tumors showed the lack of a PstI-generated 4.2-kilobase MMTV-gag-pol band. To examine the possibility of endogenous MMTV action via enhancer insertion, DNAs from DIM preneoplasms and tumors were restricted with EcoRI, BamHI, or SstI and subjected to Southern blot analysis using an MMTV-long terminal repeat probe. The normal endogenous proviral content was detected in all DIM tissues assayed; no new proviruses were found. To examine the possibility of endogenous MMTV gene product oncogenesis, MMTV transcripts were quantified by slot blot analysis and MMTV envelope proteins were assayed by immunohistochemical staining of DIM tissue sections. While all DIM tissues expressed MMTV-long terminal repeat transcripts, the level of expression did not correlate with tumorigenicity. Most frequently, MMTV-env-containing sequences were more abundant than the 1.6-kilobase long terminal repeat transcript, the latter being the most promising candidate for a MMTV gene product mediating mammary tumorigenesis. However, preneoplasms and tumors of only the DIM 4 line contained levels of MMTV Mr 52,000 or 36,000 glycoproteins detectable by immunoperoxidase staining. Electron microscopy did not reveal any virus particles in DIM 4 tissues. These data do not substantiate MMTV as a causative agent in the formation of the DIM preneoplasms or tumors. Thus while MMTV function may confuse the interpretation of causative events in the formation of other preneoplasms and neoplasms, the DIM preneoplasms represent a model system for the study of MMTV-independent mechanisms.

Animals↗
PubMed1987

Activation of endogenous MMTV proviruses in murine mammary cancer induced by chemical carcinogen.

A study was undertaken to determine whether activation of expression of silent endogenous mouse mammary tumor virus (MMTV) proviruses may occur during tumor induction by a chemical carcinogen. A series of transplantable mammary tumors induced in BALB/c mice by treatment with dimethylbenz(alpha)anthracene (DMBA), pituitary isograft, or both was examined. The results obtained suggest that chemical carcinogens may induce mammary tumors through more than one pathway. Two of 9 tumor lines produced virus-specific products at levels above those observed during the course of normal mammary gland development. One tumor contained high levels of MMTV-specific envelope [3.8 kilobase (kb)] and genomic length (8.9 kb) RNAs. This tumor expressed core- and envelope-related proteins detectable by immunoblotting (including p28, gp52, and gp36), displayed an acquired provirus with a restriction map different from those of described exogenous MMTV strains, and contained abundant virus particles. The other tumor that expressed high levels of MMTV gene products contained envelope-specific (3.8 kb) and long-terminal-repeat-specific (1.6 kb) messages but no full-length RNA. It exhibited an aberrant 39 kDa, envelope-related protein, but no virus particles. Methylation data implicated the usually silent endogenous Mtv-8 provirus as the source of the abnormal envelope protein. None of the tumors expressed RNA from the putative mammary oncogenes, int-1 or int-2. We propose that chemical carcinogens may activate different cellular genes by mutation and that, in a subset of DMBA-induced mammary tumors, the target genes include endogenous MMTV proviruses that are normally not expressed. The effect on provirus expression varies from tumor to tumor, but is stable over passage of a given tumor. MMTV may be of etiological importance in the genesis of those DMBA-induced tumors which contain high levels of MMTV-specific products, but its action in the BALB/c system is not mediated through enhanced expression of the int-1 or int-2 preferred integration regions.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Expression of differentiation-specific proteins in preneoplastic mammary tissues in BALB/c mice.

The levels of milk-specific mRNAs (alpha-casein, whey acidic protein) and proteins (casein, alpha-lactalbumin) were examined in the DIM series of mammary preneoplastic outgrowth lines and tumors. The constitutive production of casein protein was variable among the preneoplastic DIM outgrowth lines maintained in virgin mice. Outgrowth line DIM-2 consistently expressed a very low level of casein mRNA and protein but no detectable alpha-lactalbumin protein. Outgrowth line DIM-4 expressed a high level of casein protein and no alpha-lactalbumin; however, by transplant generation 9, the levels of casein mRNA and protein were significantly decreased but remained greater than those found in DIM-2. Outgrowth line DIM-3 expressed high levels of casein protein during all transplant generations examined and sporadically exhibited detectable amounts of alpha-lactalbumin. The level of beta-casein mRNA in DIM-3 was 7 times greater than seen in DIM-4 outgrowths, but still only 2% of that measured in the normal mammary gland from lactating mice. The majority of tumors derived from the DIM outgrowth lines expressed very low levels of beta-casein mRNA and total casein protein, although occasionally tumors were observed with very high levels of casein expression. Immunoblot analysis of cellular extracts indicated that alpha, beta-, and gamma-caseins were expressed in the three outgrowth lines to varying degrees. Whey acidic protein mRNA attained barely detectable levels in the best of cases. Only outgrowth line DIM-3 responded to a normal lactogenic stimulus (lactating mouse) with significantly increased levels of milk-specific products. As determined by avidin-biotin peroxidase staining, the percentage of alveoli expressing beta-casein and alpha-lactalbumin proteins in lactating mice increased from 20 and 0%, respectively, in virgin mice to 85 and 40%, respectively, in lactating mice. Similarly, the levels of mRNA for beta-casein and whey acidic protein increased 8- and 5.5-fold, respectively. These results indicate that the cell populations selected by serial transplantation of preneoplastic mammary tissues fall into at least three categories with respect to expression of mammary-specific differentiation products: uninducible, inducible, constitutive. The DIM-3 outgrowth line appears to represent a highly inducible cell population. As concluded in earlier investigations, there was no correlation between secretory activity, morphology of the outgrowths, and tumor-producing capabilities in virgin mice. The effect of a normal lactogenic stimulus on the tumor potential of the DIM-3 line is currently under investigation.

Adenocarcinoma↗
PubMed1987

Casein gene expression in mouse mammary epithelial cell lines: dependence upon extracellular matrix and cell type.

The COMMA-D mammary cell line exhibits mammary-specific functional differentiation under appropriate conditions in cell culture. The cytologically heterogeneous COMMA-D parental line and the clonal lines DB-1, TA-5, and FA-1 derived from the COMMA-D parent were examined for similar properties of functional differentiation. In monolayer cell culture, the cell lines DB-1, TA-5, FA-1, and MA-4 were examined for expression of mammary-specific and epithelial-specific proteins by an indirect immunofluorescence assay. The clonal cell lines were relatively homogeneous in their respective staining properties and seemed to represent three subpopulations found in the heterogeneous parental COMMA-D line. None of the four clonal lines appeared to represent myoepithelial cells. The cell lines were examined for expression of beta-casein mRNA in the presence or absence of prolactin. The heterogeneous COMMA-D line, but none of the clonal lines, was induced by the presence of prolactin to produce significantly increased levels of beta-casein MRNA. The inducibility of beta-casein in the COMMA-D cell line was further enhanced by a reconstituted basement membrane preparation enriched in laminin, collagen IV, and proteoglycans. Individual matrix components of laminin, fibronectin, heparan sulfate, heparan, or hyaluronic acid were not effective as substrata for the induction of beta-casein mRNA. These results support the hypothesis that the functional response of inducible mammary cell populations is a result of interaction among hormones, multiple extracellular matrix components, and specific cell types.

Animals↗
PubMed1987

Mammary preneoplasia and tumorigenesis in the BALB/c mouse: structure and modification of mouse mammary tumor virus DNA sequences.

Mouse mammary tumor virus (MMTV) DNA sequences were examined in mammary tissues from BALB/c mice, including both preneoplastic hyperplastic alveolar nodule (HAN) outgrowth lines, tumors derived from those preneoplastic tissues, and DMBA-induced mammary tumors. Over 60 different HAN and tumors samples were analyzed. The D2 HAN line contained one additional provirus, whereas Cv-2 and Cv-4 HAN lines that are infected with exogenous virus exhibited multiple virus integration events. D2 tumors showed the same provirus pattern as D2 HANs, whereas Cv-2 and Cv-4 tumors exhibited a subset of the acquired proviruses found in the parental HAN populations. Differential methylation patterns of virus-specific sequences were observed that resembled those described for other tissues in which viral DNA replication and integration has occurred, i.e., acquired proviruses were hypomethylated and endogenous proviruses were methylated. In tumors that arose from HAN lines and exhibited only endogenous proviruses, demethylation of the subgenomic Mtv-6 locus was observed. Demethylation of Mtv-6 was not detected in any of the preneoplastic tissues. Altered methylation of Mtv-8 and -9 was observed in both Cv-2 and Cv-4 tumors. Finally, mammary tumors induced by DMBA carried no acquired proviruses and demethylation of endogenous MMTV proviruses was demonstrated.

5-Methylcytosine↗
PubMed1987

Proteins antigenically related to peptides encoded by the mouse mammary tumour virus long terminal repeat sequence are associated with intracytoplasmic A particles.

Intracytoplasmic A particles (CAP), previously identified as cytoplasmic nucleocapsid precursors to mouse mammary tumour virus (MMTV), reacted strongly in immunodiffusion tests with polyclonal antibodies raised against synthetic oligopeptides derived from the open reading frame (ORF) in the long terminal repeat (LTR) of MMTV. In Western blots, several CAP proteins (p80, p72-68, p36, p32, p18-12) were reactive with polyclonal antibodies raised against three separate LTR ORF synthetic peptides. Disrupted MMTV virions did not react with the anti-LTR ORF peptides suggesting that ORF proteins were excluded from mature virions during maturation. Serial dilution of anti-LTR ORF antibody demonstrated that the most reactive CAP proteins in Western blots migrated as a doublet band with estimated molecular weights of 68,000 and 72,000. Reactivity of anti-LTR ORF serum with these and other CAP proteins was removed upon preincubation with free synthetic peptide. Absorption with LTR synthetic peptides did not affect the reactivity of antibodies directed against MMTV gag proteins with similarly sized CAP polyproteins. LTR ORF-related proteins with molecular weights similar to those associated with CAP were also detectable in Western blots of total cytoplasmic extracts of MMTV-infected mammary tumour cells.

Animals↗
PubMed1987

Mammary cancer stages in BALB/cV mice: mouse mammary tumor virus expression and virus-host interactions.

A unique subline of BALB/c mice, designated "BALB/cV," exhibits an intermediate mammary tumor incidence (47%) and harbors a distinct milk-transmitted mouse mammary tumor virus (MMTV). Virus expression and virus-host interactions were examined during the different stages of mammary tumorigenesis (normal, preneoplastic, and neoplastic) in the BALB/cV system. Protein immunoblot analyses established the presence of correctly processed (BALB/cV)MMTV structural proteins in all types of BALB/cV mammary tissues. Competition enzyme-linked immunosorbent assays demonstrated that cells from each biologic phenotype were capable of supporting high levels of (BALB/cV)MMTV protein expression. However, mammary epithelial cells that spontaneously underwent the inappropriate pathway of squamous metaplasia did not contain detectable levels of (BALB/cV)MMTV structural proteins. Iodination experiments revealed the presence of a 68K env-related protein on the surface of BALB/cV mammary cells. Nevertheless, sera from 40 mice bearing BALB/cV-positive mammary tissues did not contain detectable levels of anti-env antibodies. Metabolic labeling experiments showed that the half-life of transformation-related, host cell protein p53 (approximately equal to 60 min) in the distinct BALB/cV mammary cell populations was similar to that reported for normal mouse 3T3 cells. It appears that p53 is not stabilized by protein interactions involving any MMTV-encoded or MMTV-induced protein in mammary tumor cells. These characteristics of the BALB/cV system are compatible with the hypothesis that MMTV is only one of two or more cooperating factors required to mediate complete mammary transformation.

Animals↗
PubMed1987

Enhancement of tumorigenicity with morphological progression in a BALB/c preneoplastic outgrowth line.

Four newly established mammary hyperplastic outgrowth lines were analyzed for their tumorigenic, morphological, and ovarian hormone-dependent growth properties in BALB/cMed mice. The mammary outgrowth lines were designated DIM-1, DIM-2, DIM-3, and DIM-4 to indicate their origin from the mammary cell line COMMA-D. DIM-1, DIM-2, and DIM-3 were classical hyperplastic alveolar outgrowth lines that possessed high tumor-producing capabilities and rapidly evolved by transplant generation (TG) 6 into ovarian hormone-independent populations. DIM-3 was also characterized by extensive formation of dilated (cystic) alveoli. This characteristic did not correlate either positively or negatively with the tumor-producing capabilities of these lines. DIM-4 was a ductal outgrowth line that exhibited a progression in several biological properties. This line progressed morphologically from a ductal outgrowth to a mixed outgrowth of small ducts (ductules) with scattered alveoli and then in subsequent passages to a uniform alveolar outgrowth. Concurrent with these morphological changes, the tumor-producing capabilities of DIM-4 increased from low [40% with the time for 50% of the transplants to produce mammary tumors (TE50) greater than 12 mo] to high (71% with a TE50 of 7.1 mo). The ductal outgrowth line (TG 4) was totally dependent on ovarian hormones for growth; however, later passages (TG 8) of DIM-4 were only partially ovarian hormone dependent for growth and ovarian hormone independent for maintenance of alveolar morphology. In addition, the tumorigenic response to 7,12-dimethylbenz[a]anthracene (CAS: 57-97-6) was low in the ductal stage (TG 4) and high in the alveolar stage (TG 7). The results demonstrate an enhancement of tumorigenicity with morphological and biological progression in a preneoplastic mammary cell population and support the hypothesis that the cells at high risk for tumorigenesis in the BALB/c mammary gland appear to be the alveolar cell type.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Mechanisms of selenium inhibition of tumorigenesis.

Numerous experiments have demonstrated that selenium supplementation to the diet at modest and nontoxic levels is an effective inhibitor of mammary tumorigenesis in mice and rats. In mice, selenium is most effective during the early stages of tumorigenesis, in particular the events surrounding the induction and expression of the preneoplastic transformation. Whereas selenium is an effective chemopreventive agent, there is little data to support its role as an effective therapeutic agent. The mechanisms of selenium-mediated inhibition of tumorigenesis have not been established. However, the available data suggest that selenium does not act by way of the principal selenoprotein in the cell, glutathione peroxidase, nor does selenium inhibit lipid peroxidation. A number of different mechanisms to explain the inhibitory effects of selenium are discussed; however, definitive answers await further experiments.

Animals↗
PubMed1986

Differential expression of endogenous mouse mammary tumor virus genes during development of the BALB/c mammary gland.

Expression of endogenous mouse mammary tumor virus sequences varied over the course of development of the mammary gland during primary pregnancy and lactation in virus-free BALB/c mice. Although RNA from all regions of the genome was detected, both the level and temporal regulation of expression were different for long terminal repeat-, env-, and gag-pol-specific RNAs. Analysis of the methylation status of proviral DNA indicated differential accessibility of the three endogenous units during development. The results demonstrated noncoordinate regulation of mouse mammary tumor virus expression with respect to provirus template utilized and specific transcripts accumulated.

Animals↗
PubMed1986

Properties of mouse mammary epithelial cell lines characterized by in vivo transplantation and in vitro immunocytochemical methods.

Immunocytochemical and in vivo transplantation methods were used to study the characteristics of a series of newly developed mammary epithelial cell lines. These mouse mammary cell lines were derived from mid-pregnant primiparous BALB/c female mice and were routinely grown in Dulbecco's modified Eagle medium supplemented with 1% fetal bovine serum, insulin, transferrin, epidermal growth factor, and selenite. Of the 6 cell lines, 1 cell line, COMMA-D, produced normal and preneoplastic mammary outgrowths when it was transplanted into mammary fat pads of syngeneic mice. One cell line, MOD, produced only mammary adenocarcinomas. The other 4 cell lines, COMMA-F, COMMA-T, MOMA-1, and MOMA-2, produced neither normal nor neoplastic outgrowths. Immunocytochemical staining with polyclonal antibodies to keratin and vimentin intermediate filament proteins revealed that 5 of the 6 cell lines were epithelial. The sixth cell line, MOMA-2, was apparently of fibroblastic origin. The COMMA-D cell line was unique compared to the other cell lines with respect to several characteristics. The cell line was morphologically heterogeneous as determined by phase-contrast microscopy, cytologically heterogeneous as determined by immunocytochemical staining, and heterogeneous with respect to DNA content. Finally, the full morphogenic potential of COMMA-D included not only normal mammary ductal and preneoplastic mammary alveolar outgrowths but also adenocarcinomas and fibrosarcomas. The expression of this morphogenic potential upon transplantation in vivo was drastically diminished after passage 14. The significance of the cellular heterogeneity with respect to expression of mammary-specific morphogenesis is not understood at this time; however, conceivably, the observed heterogeneity reflects an essential requirement for morphogenesis in vivo. The transplantation and immunocytochemical characteristics provide the descriptive basis for further studies on these cell lines to determine the cell lineages involved in morphogenesis and preneoplastic transformation in vivo.

Animals↗
PubMed1986

Distribution of selenoproteins in mouse mammary epithelial cells in vitro and in vivo.

Resolution of selenium-containing proteins synthesized by mouse mammary gland cells was achieved using the technique of two-dimensional gel electrophoresis. Radioactive selenium as H2[75Se]O3 was incorporated into relatively few proteins within mammary gland cells maintained in vitro and cells of mammary gland tissue in vivo. The pattern of selenoproteins obtained was identical qualitatively between a nontumorigenic differentiated cell line, COMMA-D, and a tumorigenic cell line, MOD. Eleven selenoproteins ranging in molecular weight from 12,000-78,000 were detected and a total of 25 spots were visible indicating charge heterogeneity of some of the proteins. A major selenoprotein (Mr 26,000) migrated identically with the subunit form of glutathione peroxidase, a well-characterized protein containing four selenocysteine residues. Other major selenoproteins had molecular weights of 58,000, 22,000, 18,000, and 14,000. Analysis of the total cellular protein extract and of each of the five major proteins indicated that selenium was incorporated as selenocysteine in the proteins. Incorporation of selenium as selenomethionine into cellular proteins was detected only when selenomethionine was provided in the culture medium. Cleavage of 75Se-labeled proteins with N-chlorosuccinimide produced polypeptides of different molecular weights indicating that the Mr 58,000, 26,000, and 22,000 selenoproteins were dissimilar in the amino acid sequences containing the selenoamino acid. The pattern of selenoproteins of mammary gland cells in vivo was similar to that obtained for cells in culture and most other tissues in vivo. These results provide evidence for the presence of multiple selenium-containing proteins in mammary epithelial cells. The possible significance of these proteins in selenium-mediated inhibition of cell growth awaits future clarification.

Animals↗
PubMed1985

Comparative analysis of casein synthesis during mammary cell differentiation in collagen and mammary gland development in vivo.

Substrata upon which epithelial cells are cultured modulate their morphology,growth, and ability to differentiate. Mouse mammary epithelial cells cannot be induced to synthesize caseins, a marker of cell differentiation, when grown on a plastic surface. An analysis was made of the effect of time within a collagen matrix on the ability of normal mammary epithelial cells to be induced to synthesize caseins and that response was compared to mammary gland development in vivo. Primary cultures of mammary cells from unprimed virgin BALB/c mice were embedded in rat-tail collagen gel mixtures and maintained in growth medium. Induction medium containing lactogenic hormones was added at various times. The cells were monitored every 3-7 days over a period of 8 weeks for cell growth, casein synthesis, and ability to grow in vivo in cleared mammary fat pads. Casein accumulation was assayed quantitatively by an ELISA competition assay and qualitatively by the immunoblot procedure using specific antisera prepared against purified mouse caseins. No marked differences in cell numbers and transplantability potential were observed among cells cultured for various times in collagen. Mammary cells grown in collagen for up to 8 weeks retained the capacity to grow in vivo as normal ductal outgrowths. The duration of culture within collagen prior to hormonal stimulation did influence the kinetics of casein synthesis. Cells cultured for 1 week in growth medium did not accumulate detectable levels of casein until after 3 weeks of induction, whereas cells cultured for 2 or 4 weeks responded by accumulating caseins after 2 weeks and 3 days of induction, respectively. While the levels of total caseins that accumulated under optimal conditions of induction in culture approached levels found during lactation in vivo, the relative proportion of specific casein polypeptides synthesized in culture was altered from alpha casein (43K) in favor of the beta casein (30K) species. These results suggest that a period of culture within collagen is required to permit mammary epithelial cells to become responsive for hormone-induced differentiation. It is possible that during growth within the collagen the cells synthesize and deposit extracellular matrix components important in modulating gene expression.

Animals↗
PubMed1985

Molecular basis of altered mouse mammary tumor virus expression in the D-2 hyperplastic alveolar nodule line of BALB/c mice.

The preneoplastic D-2 hyperplastic outgrowth line, which was derived from a hormone-induced hyperplastic alveolar nodule (HAN) of a BALB/c mouse, was used for a detailed analysis of mouse mammary tumor virus (MMTV) expression. The D-2 HAN line has previously been shown to express viral RNA representative of the entire genome, although viral particles have been noted only rarely. The MMTV-specific mRNA, protein, and DNA content of the D-2 tissues was defined in an effort to better understand the molecular basis of the aberrant virus expression. Northern blotting techniques demonstrated the presence of properly processed 8.9 kb (genomic) and 3.6 kb (envelope) mRNA. Protein electroblotting procedures established the presence of properly processed viral core protein p28. In contrast, the envelope precursor polyprotein was not processed into detectable levels of gp52. Analysis of MMTV proviral content by Southern blot methodology revealed the presence of a newly acquired provirus which serves as a marker for the clonal nature of the D-2 line. The origin of the new provirus is unknown. Methylation studies established that the new proviral insert is hypomethylated and, therefore, is likely serving as the template for the MMTV expression observed in the D-2 HAN line. These characteristics of the D-2 line make it an excellent system in which to study the role, if any, of MMTV in the progression of D-2 preneoplastic tissues to the tumor phenotype.

Animals↗