title: Cooperation of hTERT, SV40 T antigen and oncogenic Ras in tumorigenesis: a cell transplantation model using bovine adrenocortical cells.
abstract: Expression of TERT, the reverse transcriptase component of telomerase, is necessary to convert normal human cells to cancer cells. Despite this, "telomerization" by hTERT does not appear to alter the normal properties of cells. In a cell transplantation model in which bovine adrenocortical cells form vascularized tissue structures beneath the kidney capsule in scid mice, telomerization does not perturb the functional tissue-forming capacity of the cells. This cell transplantation model was used to study the cooperation of hTERT with SV40 T antigen (SV40 TAg) and oncogenic Ras in tumorigenesis. Only cells expressing all three genes were tumorigenic; this required large T, but not small t, antigen. These cells produced a continuously expanding tissue mass; they were invasive with respect to adjacent organs and eventually destroyed the kidney. Cells expressing only hTERT or only Ras produced minimally altered tissues. In contrast, SV40 TAg alone produced noninvasive nodules beneath the kidney capsule that had high proliferation rates balanced by high rates of apoptosis. The use of cell transplantation techniques in a cell type that is able to form tissue structures with or without full neoplastic conversion allows the phenotypes produced by individual cooperating oncogenes to be observed.
authors.affiliation: Huffington Center on Aging, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suwa
authors.forename: Lianqing
authors.initials: L
authors.lastname: Yang
authors.forename: Lifang
authors.initials: L
authors.lastname: Zhao
authors.forename: Christina L
authors.initials: CL
authors.lastname: Hawks
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hornsby
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D015153:Blotting, Western; D002417:Cattle; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D002472:Cell Transformation, Viral / Q000235:genetics; D017690:Cell Transplantation; D002478:Cells, Cultured / Q000473:pathology; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008954:Models, Biological; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D019098:Telomerase / Q000502:physiology*; D014162:Transfection
chemical_list: D000952:Antigens, Polyomavirus Transforming; D004268:DNA-Binding Proteins; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)