Development of resistance to insulin-like growth factor binding protein-3 in transfected T47D breast cancer cells.
Insulin-like growth factor binding protein-3 (IGFBP-3) has antiproliferative effects in many cell types but paradoxical growth stimulation has also been reported. In early passages following transfection of T47D breast cancer cells with IGFBP-3 cDNA, the proliferation rate and serum-stimulated DNA synthesis were significantly reduced compared to control cells. Cell cycle analysis indicated that growth-inhibited IGFBP-3-producing cells accumulated in G1 phase. After several passages, the transfected cells became resistant to the inhibitory effects of IGFBP-3 and showed transiently enhanced proliferation rates despite an increased IGFBP-3 concentration in the medium. IGFBP-3 proteolysis did not account for its decreased antiproliferative activity in resistant cells. We hypothesize that development of resistance to the antiproliferative action of IGFBP-3 might be an important step in the malignant progression of breast cancer cells.
Firth
S M
SM
Kolling Institute of Medical Research, University of Sydney, New South Wales, Australia. sfirth@med.usyd.edu.au
Fanayan
S
S
Benn
D
D
Baxter
R C
RC
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics* / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D006131:Growth Inhibitors; D018972:Insulin-Like Growth Factor Binding Protein 3