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Malignant transformation of human fibroblast strain MSU‐1.1 by v‐fes requires an additional genetic change
Author(s) -
Lin Chiencheng,
Maher Veronica M.,
McCormick J. Justin
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910630125
Subject(s) - oncogene , transfection , biology , microbiology and biotechnology , malignant transformation , plasmid , fibroblast , transformation (genetics) , gene , strain (injury) , cell culture , cancer research , genetics , cell cycle , anatomy
To determine whether the v‐fes oncogenc can malignantly transform human fibroblasts that have acquired an infinite life span and are partially growth‐factor‐independent, we trans‐fected cell strain MSU‐1.1 with a plasmid containing the v‐fes oncogene and a bacterial histidinol dehydrogenase gene. Of the 60 independent histidinol‐resistant clones isolated and assayed for v‐fes expression using a fes‐specific monoclonal antibody, 6 were found to express the v‐fes protein at a detectable level. When progeny cells from these 6 clones were further characterized, 3 of the 6 clonal populations exhibited a significant increase in the ability to form medium‐sized colonies in agarose, but none were tumorigenic in athymic mice. However, when the 6 populations were propagated for many generations, the same 3 populations acquired the ability to form very large colonies in agarose (± 100 μm in diameter) at a frequency of 2% to 17%, and formed malignant tumors in athymic mice. This suggests that an additional genetic change required for malignant transformation had been spontaneously acquired in 3 of the v‐fes ‐transformed cell strains. To determine whether the change or changes were the equivalent of an activated sis or ras proto‐oncogene, we transfected the v‐fes oncogene into derivative strains of MSU‐1.1 that express a transfected v‐sis, c‐H‐ras or c‐N‐ras oncogene, but that do not form tumors, and assayed the v‐fes‐expressing transfectants for tumorlgenicity. The results showed that when complemented either by a ras oncogene expressed at a somewhat enhanced level or by the v‐sis oncogene, v‐fes can supply the additional change required for malignant transformation.