Gene expression profiling to identify oncogenic determinants of autocrine human growth hormone in human mammary carcinoma

Xiu Qin Xu, B. Starling Emerald, Eyleen L.K. Goh, Nagarajan Kannan, Lance D. Miller, Peter D. Gluckman, Edison T. Liut, Peter E. Lobie

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

We have exploited a discrepancy in the oncogenic potential of autocrine and exogenous human growth hormone (hGH) in an attempt to identify molecules that could potentially be involved in oncogenic transformation of the human mammary epithelial cell. Microarray analysis of 19,000 human genes identified a subset of 305 genes in a human mammary carcinoma cell line that were remarkably different in their response to autocrine and exogenous hGH. Autocrine and exogenous hGH also regulated 167 common genes. Semiquantitative reverse transcription-PCR confirmed differential regulation of genes by either autocrine or exogenous hGH. Functional analysis of one of the identified autocrine hGH-regulated genes, TFF3, determined that its expression is sufficient to support anchorage-independent growth of human mammary carcinoma cells. Small interfering KNA-mediated knockdown of TFF3 concordantly abrogated anchorage-independent growth of mammary carcinoma cells and abrogated the ability of autocrine hGH to stimulate oncogenic transformation of immortalized human mammary epithelial cells. Further functional characterization of the identified subset of specifically autocrine hGH regulated genes will delineate additional novel oncogenes for the human mammary epithelial cell.

Original languageEnglish (US)
Pages (from-to)23987-24003
Number of pages17
JournalJournal of Biological Chemistry
Volume280
Issue number25
DOIs
StatePublished - Jun 24 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Xu, X. Q., Emerald, B. S., Goh, E. L. K., Kannan, N., Miller, L. D., Gluckman, P. D., Liut, E. T., & Lobie, P. E. (2005). Gene expression profiling to identify oncogenic determinants of autocrine human growth hormone in human mammary carcinoma. Journal of Biological Chemistry, 280(25), 23987-24003. https://doi.org/10.1074/jbc.M503869200