¹Cell Biology Laboratory, Department of Biochemistry, BioSciences Institute, National University of Ireland, Cork, Ireland

Correspondence: R O'Connor, r.oconnor@ucc.ie

Received 24 February 2005; Revised 14 April 2005; Accepted 20 April 2005; Published online 6 June 2005.

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, igH3, mts1, igfbp5 protease, and mystique; (2) cell division, including cyclin A1 and cdk1; (3) signal transduction, including pkcbp 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.