Malignant transformation of NIH 3T3 fibroblasts by human c-sis is dependent upon the level of oncogene expression.

Abstract:

:High-level expression of the c-sis oncogene, which encodes the beta chain of platelet-derived growth factor, transforms immortalized rodent fibroblasts in vitro to a malignant phenotype. c-sis gene expression has been demonstrated in a variety of human tumors, although generally at levels much lower than those shown to transform cells in vitro. We examined the effect of lower levels of c-sis expression on the phenotype of NIH 3T3 fibroblasts. Clones with various levels of c-sis expression were generated by transfecting NIH 3T3 cells with a plasmid that expressed the human c-sis cDNA and the TN5 neomycin-resistance gene. G418-resistant clones, which expressed the c-sis cDNA, were selected and characterized. Alterations in the phenotype of the clones that expressed c-sis ranged from increased growth in soft agar to malignant tumor formation in nude and syngeneic mice. Increased levels of c-sis cDNA expression correlated with the acquisition of features of transformation in a dose-dependent manner and altered the cellular phenotype in a manner consistent with the progression of cells towards malignancy. These data support a model in which low levels of sis gene expression in tumors contribute to the acquisition of some features of transformation but require complementation by other genes or factors to produce a fully malignant phenotype.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

MacArthur LH,Clarke MF,Westin EH

doi

10.1002/mc.2940050412

subject

Has Abstract

pub_date

1992-01-01 00:00:00

pages

311-9

issue

4

eissn

0899-1987

issn

1098-2744

journal_volume

5

pub_type

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