Development of Resistance to Insulin-like Growth Factor Binding Protein-3 in Transfected T47D Breast Cancer Cells

详细信息    查看全文

• 作者：Firth ; Sue M. ; Fanayan ; Susan ; Benn ; Diana ; Baxter ; Robert C.
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：1998
• 出版时间：May 19, 1998
• 年：1998
• 卷：246
• 期：2
• 页码：325-329
• 全文大小：144 K

文摘

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 G₁phase. 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.