Telomerase is not required for experimental tumorigenesis of human and bovine adrenocortical cells.
Telomerase has often been thought to be essential for tumorigenesis of human cells. Adrenocortical cancers, like other cancers, typically have telomerase activity. We reinvestigated the requirement for telomerase in the conversion of normal human and bovine adrenocortical cells to cancer cells. When primary adrenocortical cells were transduced with retroviruses encoding SV40 large T antigen and Ha-RasG12V and immediately transplanted into immunodeficient mice they produced invasive and metastatic tumors. Cells had negligible telomerase activity before transplantation and after recovery from tumors. However, these tumors were not immortal and cells entered crisis, limiting further growth of the tumor as well as invasion and metastasis. Infection of these tumor cells with a retrovirus encoding hTERT restored growth in culture and restored the malignant properties of the cells in immunodeficient animals. These experiments differ from previous studies in which telomerase was found to be essential for tumorigenicity: 1) we used tissue reconstruction techniques for introduction of cells into host animals and 2) we infected primary cells with retroviruses and immediately transplanted them without drug selection.
Chen
Meizhen
M
Department of Physiology and Sam and Ann Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, Texas, USA.
Hawks
Christina L
CL
Huang
Qin
Q
Sun
Beicheng
B
Hornsby
Peter J
PJ
D000302:Adrenal Cortex / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D015197:Carcinogenicity Tests; D002417:Cattle; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D015870:Gene Expression; D011905:Genes, ras; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D019098:Telomerase / Q000378:metabolism*; D014161:Transduction, Genetic
D000952:Antigens, Polyomavirus Transforming; D019098:Telomerase