Premium
Neoplastic conversion of human colon smooth muscle cells: No requirement for telomerase
Author(s) -
Liang Sitai,
Kahlenberg Morton S.,
Rousseau Dennis L.,
Hornsby Peter J.
Publication year - 2008
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20405
Subject(s) - biology , telomerase , telomerase reverse transcriptase , cancer research , oncogene , cell culture , cancer cell , cancer , transduction (biophysics) , transfection , antigen , gene , microbiology and biotechnology , immunology , genetics , cell cycle , biochemistry
The role of telomerase as an essential requirement for the neoplastic conversion of human cells has been controversial. In the model of conversion of normal human cells to cancer cells by the combination of simian virus 40 (SV40) early region genes and oncogenic Ras (H‐Ras G12V ), telomerase (hTERT) was originally described as essential in conjunction with these other genes. Here we used primary cultures of colon smooth muscle cells isolated from surgical specimens. SV40 large T antigen (TAg) and oncogenic Ras G12V were introduced into the cells by retroviral transduction and cells were rapidly transplanted into the subrenal capsule space in immunodeficient mice, without selection in culture. Malignant tumors were formed from transduced cells. Extensive invasion into the kidney occurred even when tumors were small; in contrast, at the same tumor size, oncogene‐expressing fibroblasts did not show much invasion. Increased invasiveness was also observed in vitro. However, cells in these cancers showed morphological evidence of crisis, consistent with their lack of telomerase. These experiments on human colon smooth muscle cells support the concept that Ras G12V and SV40 TAg form a minimal set of genes that can convert normal human cells to cancer cells without a requirement for hTERT. © 2007 Wiley‐Liss, Inc.