Neoplastic conversion of human colon smooth muscle cells: No requirement for telomerase.

Abstract:

: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.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Liang S,Kahlenberg MS,Rousseau DL Jr,Hornsby PJ

doi

10.1002/mc.20405

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

478-84

issue

6

eissn

0899-1987

issn

1098-2744

journal_volume

47

pub_type

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