Gene expression profiles in cells transformed by overexpression of the IGF-I receptor

Abstract

To identify genes associated with insulin-like growth factor-I receptor (IGF-IR)-mediated cellular transformation, we isolated genes that are differentially expressed in R⁻ cells (derived from the IGF-IR knockout mouse) and R⁺ cells (R⁻ cells that overexpress the IGF-IR). From these, 45 genes of known function were expressed at higher levels in R⁺ cells and 22 were expressed at higher levels in R⁻ cells. Differential expression was confirmed by Northern blot analysis of R⁺ and R⁻ cells. Genes expressed more abundantly in R⁺ cells are associated with (1) tumour growth and metastasis including, βigH3, mts1, igfbp5 protease, and mystique; (2) cell division, including cyclin A1 and cdk1; (3) signal transduction, including pkcδbp and lmw-ptp; and (4) metabolism including ATPase H⁺ transporter and ferritin. In MCF-7 cells IGF-I induced expression of two genes, lasp-1 and mystique, which could contribute to metastasis. Lasp-1 expression required activity of the PI3-kinase signalling pathway. Mystique was highly expressed in metastatic but not in androgen-dependent prostate cancer cell lines and Mystique overexpression in MCF-7 cells promoted cell migration and invasion. We conclude that genes identified in this screen may mediate IGF-IR function in cancer progression.