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

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, beta ig H3, mts1, igfbp5 protease, and mystique; ( 2) cell division, including cyclin A1 and cdk1; ( 3) signal transduction, including pkc delta bp 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.