differential effect of growth factors on invasion and proliferation of endocrine resistant breast cancer cells微分作用的生长因子入侵和内分泌抗乳腺癌细胞扩散.pdfVIP

Differential Effect of Growth Factors on Invasion and Proliferation of Endocrine Resistant Breast Cancer Cells 1 2 1 1 Maitham A. Khajah , Sanaa Al Saleh , Princy M. Mathew , Yunus A. Luqmani * 1 Faculty of Pharmacy, Kuwait University, Safat, Kuwait, 2 Faculty of Medicine, Kuwait University, Safat, Kuwait Abstract We have established several breast cancer cell lines that exhibit a permanent ER-depleted phenotype, induced by shRNA transfection of MCF-7 cells, which afford a useful model for studying acquired endocrine resistance. Previously we showed that MDA-231 as well as ER-silenced cells could invade through simulated extracellular matrix components. However, the contribution of individual serum components responsible for cell invasion was not determined. In the present study, an under-agarose gel assay was used to quantitatively assess the invasive movement of two ER-silenced cell lines (pII and YS2.5) in comparison to the parental MCF-7, the ER negative MDA-231, and normal HBL100 cells, as well as a line that was ER-shRNA transfected but failed to exhibit ER down-regulation (YS1.2). We also examined the effect of the growth factors EGF, IGF-1, TGFb, PDGFC and RANTES on pII cell invasion and proliferation. All breast cancer cell lines which had reduced ER expression exhibited a serum-dependent invasive ability related to the degree of induced ER loss. TGFb treatment inhibited pII cell proliferation and enhanced their invasive ability but at a relatively high dose. IGF-1 and EGF enhanced pII cell proliferation, with the latter playing the major role in promoting cell invasion. PDGFC did not affect either process although it is highly expressed in pII cells. Differential effects were observed on activa