Overexpression of adrenomedullin gene markedly inhibits proliferation of PC3 prostate cancer cells in vitro and in vivo

Ibane Abasolo, Luping Yang, Riffat Haleem, Wuhan Xiao, Ruben Pio, Frank Cuttitta, Luis M. Montuenga, James M. Kozlowski, Alfonso Calvo, Zhou Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The expression of the gene encoding adrenomedullin (AM), a multifunctional peptide hormone, in the prostate is localized to the epithelial cells. Prostate cancer cells are derived from prostatic epithelial cells. To elucidate the potential role of the AM gene in prostate cancer progression, we have stably-transfected the PC3 human prostate cancer cell line with an AM gene expression vector. The AM-transfected PC3 sublines were studied along with parental and empty vector transfected PC3 cells as controls. The average level of AM in the conditioned media of AM-transfected cells was 0.959±0.113 nM, a physiologically relevant concentration. The ectopic expression of AM gene inhibited the proliferation of PC3 cells in culture dishes. In addition, anchorage-independent growth of the transfected sublines was virtually abolished in soft agar assays. Flow cytometry studies showed that overexpression of AM gene caused a very significant G1/G0 cell cycle arrest. In vivo experiments demonstrated that AM gene expression markedly inhibited the growth of xenograft tumors in nude mice. Our in vivo and in vitro studies suggest that AM could strongly suppress the malignancy of prostate cancer cells, via autocrine and/or paracrine mechanisms.

Original languageEnglish (US)
Pages (from-to)179-187
Number of pages9
JournalMolecular and Cellular Endocrinology
Volume199
Issue number1-2
DOIs
StatePublished - Jan 31 2003

Keywords

  • Adrenomedullin
  • Growth inhibition
  • PC3
  • Prostate cancer
  • Xenograft

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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