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

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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.

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Acknowledgements

This work was funded by Tanaud Ireland Inc., Higher Education Authority of Ireland, Cancer Research Ireland, and Science Foundation Ireland. We are grateful to Kurt Tidmore for preparing the illustrations.

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Authors and Affiliations

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

    Gary Loughran, Merei Huigsloot, Patrick A Kiely, Loraine M Smith, Suzanne Floyd, Veronica Ayllon & Rosemary O'Connor

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  1. Gary Loughran
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  2. Merei Huigsloot
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  3. Patrick A Kiely
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Correspondence to Rosemary O'Connor.

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Loughran, G., Huigsloot, M., Kiely, P. et al. Gene expression profiles in cells transformed by overexpression of the IGF-I receptor. Oncogene 24, 6185–6193 (2005). https://doi.org/10.1038/sj.onc.1208772

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