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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)6185-6193
Number of pages9
JournalOncogene
Volume24
Issue number40
DOIs
Publication statusPublished - 8 Sep 2005
Externally publishedYes

Keywords

  • Apoptosis
  • Cancer
  • IGF-I receptor
  • Lasp-1
  • Mystique
  • Transformation

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