Biomedical subjects

J Trent

Publications and source records attributed to J Trent.

62 records · Page 4Linked to original sources

PubMed1986

Enhanced expression of epidermal growth factor receptor correlates with alterations of chromosome 7 in human pancreatic cancer.

Recently, the gene for the epidermal growth factor (EGF) receptor has been mapped to chromosome 7p, the short arm of chromosome 7 [Shimizu, N., Kondo, I., Gamou, M. A., Behzadian, A. & Shimizu, Y. (1984) Somatic Cell Mol. Genet. 10, 45-53]. Utilizing EGF binding in saturation studies, karyology, and cDNA hybridization experiments, we have sought to determine whether there is a correlation between dosage or alteration of chromosome 7 and enhanced expression of EGF receptor in cultured human pancreatic carcinoma cells. Saturation binding studies with 125I-labeled EGF were performed at 4 degrees C with four established human pancreatic cancer cell lines: T3M4, PANC-1, COLO 357, and UACC-462. Analysis of binding data revealed enhanced numbers of EGF receptors in all four cell lines. Chromosome banding analysis revealed clonal structural alterations of chromosome 7p in the cell lines T3M4, PANC-1, and COLO 357, whereas UACC-462 displayed multiple copies of chromosome 7. Hybridization studies using a radiolabeled EGF receptor cDNA probe failed to demonstrate DNA sequence amplification in any cell line but confirmed the presence of EGF receptor mRNA in these cells in approximate proportion to EGF receptor number. Our results suggest that enhanced expression of EGF receptor in human pancreatic cancer can be associated with either structural or numerical alterations of chromosome 7.

Cell Line↗

PubMed1986

Evidence for rearrangement, amplification, and expression of c-myc in a human glioblastoma.

Amplified cellular genes are frequently manifested in one of two cytologically recognizable forms, double minutes or homogeneously staining regions. Additionally, evidence is accumulating that aberrant expression of cellular genes (including oncogenes) may be mediated by gene amplification. We now describe the amplification and expression of the cellular oncogene c-myc in double-minute-containing cells from a patient with glioblastoma multiforme, and we have shown that the amplification is associated with rearrangement of the c-myc gene. This finding further supports the common association of the myc gene family in neurogenic tumors and provides evidence of myc gene amplification in human brain cancer.

Cell Line↗

PubMed1985

Nonrandom chromosome alterations in rhabdomyosarcoma.

Chromosome banding analysis was attempted on tumor cells from a total of six rhabdomyosarcomas. Results revealed a variety of chromosome alterations, including frequent structural rearrangement of chromosome #1 and the finding in one patient of multiple double minutes. The single chromosome most consistently involved in structural rearrangements was #3. Simple deletion or translocation of either the long or short arm of chromosome #3 was found in all rhabdomyosarcoma tumors examined in this report. Further, a review of the limited previous literature on rhabdomyosarcoma provided further support for the frequent alteration of chromosome #3 in this disease. Results from our study provide preliminary evidence that alterations of chromosome 3p14-21 may represent a site of nonrandom chromosome change in rhabdomyosarcoma.

Chromosome Aberrations↗

PubMed1981

Genetic variation in erythrocyte NAD levels in the mouse and its effect on glyceraldehyde phosphate dehydrogenase activity and stability.

During a screening of inbred strains for enzyme variation in glycolysis, differences were found in glyceraldehyde phosphate dehydrogenase (GAPDH) activity between C57BL/6J and SM/J mice. Segregation analysis did not reveal unequivocal monogenic inheritance. Dialysis of hemolysates caused decay of enzyme activity, especially in C57BL animals, which could be prevented by the presence of NAD. This led to the finding that erythrocyte NAD levels were threefold higher in SM than C57BL animals and, although additively inherited, did not appear to be monogenic. This is comparable with but independent of the differences and effect of erythrocyte NADP levels on glucose-6 phosphate dehydrogenase activity reported by R. P. Erickson (1974) Biochem. Genet. 11:33] and emphasizes the range of mechanisms that can be involved in the genetic control of enzyme activity in mammalian systems.

Animals↗

PubMedDate not supplied

Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour.

Amplified cellular genes in mammalian cells frequently manifest themselves as double minute chromosomes (DMs) and homogeneously staining regions of chromosomes (HSRs). With few exceptions both karyotypic abnormalities appear to be confined to tumour cells. All vertebrates possess a set of cellular genes homologous to the transforming genes of RNA tumour viruses, and there is circumstantial evidence that these cellular oncogenes are involved in tumorigenesis. We have recently shown that DMs and HSRs in cells of the mouse adrenocortical tumour Y1 and an HSR in the human colon carcinoma COLO320 contain amplified copies of the cellular oncogenes c-Ki-ras and c-myc, respectively. Both DMs and HSRs are found with remarkable frequency in cells of human neuroblastomas. We show here that a DNA domain detectable by partial homology to the myc oncogene is amplified up to 140-fold in cell lines derived from different human neuroblastomas and in a neuroblastoma tumour, but not in other tumour cells showing cytological evidence for gene amplification. By in situ hybridization we found that HSRs are the chromosomal sites of the amplified DNA. The frequency with which this amplification appears in cells from neuroblastomas and its apparent specificity raise the possibility that one or more of the genes contained within the amplified domain contribute to tumorigenesis.

Cell Line↗

PubMedDate not supplied

Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc.

Cellular oncogenes comprise a class of genes whose aberrant expression or function may be involved in the development of tumours. Indeed, several naturally occurring animal and human tumours are associated with consistent alterations in the structure or genomic position of particular cellular oncogenes. Recently, we isolated a DNA segment having limited similarity to c-myc (termed N-myc) from a human neuroblastoma cell line. Although N-myc was present as a single copy in normal cells, it was selectively amplified up to 140-fold in tumour cells from human neuroblastomas. Now, we have used somatic cell hybrids to show that N-myc is normally localized on the distal short arm of chromosome 2, and in situ hybridization to localize N-myc to chromosome 2p23-24. Further, in situ hybridization localizes amplified N-myc in neuroblastoma cells to homogeneously staining regions (HSRs) on different chromosomes. Thus, our results suggest that amplification and translocation of N-myc may be interrelated processes associated with human neuroblastoma, and demonstrate that the site of N-myc amplification is quite variable and bears no apparent relationship to either the normal single-copy locus or recognized sites of non-random chromosome alteration in human neuroblastoma.

Chromosome Mapping↗

PubMedDate not supplied

Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines.

The multidrug-resistance phenotype expressed in mammalian cell lines is complex. Cells selected with a single agent can acquire cross-resistance to a remarkably wide range of compounds which have no obvious structural or functional similarities. The basis for cross-resistance seems to be a decreased net cellular accumulation of the drug involved, and has been attributed to alterations in the plasma membrane. An over-expressed plasma membrane glycoprotein of relative molecular mass (Mr) 170,000 (P-glycoprotein) is consistently found in different multidrug-resistant human and animal cell lines, and in transplantable tumours. Consequently, it has been postulated that P-glycoprotein directly or indirectly mediates multidrug resistance. Here we report the cloning of a complementary DNA encoding P-glycoprotein. Southern blot analysis of hamster, mouse and human DNA using this cDNA as a probe showed that P-glycoprotein is conserved and is probably encoded by a gene family, and that members of this putative family are amplified in multidrug-resistant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Cellular and genetic properties of two melanoma cell lines established from the same tumor.

We report here the detailed cellular and genetic analysis of two new human melanoma cell lines established from the same tumor biopsy. Although derived from the same tumor biopsy, the two lines differed in their method of in vitro culture establishment with one line (HA-A) grown first in agar culture and then transferred to liquid culture, while the second cell line (HA-L) was established directly from cells grown in liquid culture. Detailed characterization of both cell lines was performed using techniques to analyze their cytogenetic, surface marker, morphology (light and electron microscopy), growth (in agar and in nude mice), and drug sensitivity profiles in comparison to the original tumor biopsy. Our results revealed no significant biologic or genetic difference between the two cell lines established by different culture techniques. Our results suggest that in some cases agar culture prior to liquid culture may be useful in establishment of human tumor cell lines.

Antigens, Neoplasm↗