PTHrP is a novel mediator for TGF-β-induced apoptosis

Yanna Cao, Weili Zhang, Xuxia Gao, Guohua Zhang, Miriam Falzon, Courtney M. Townsend, Mark R. Hellmich, Tien C. Ko

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Parathyroid hormone-related protein (PTHrP) is a polyhormone secretory protein that plays fundamental roles in the development and function of various tissues. Transforming growth factor (TGF)-β is an important tumor suppressor that induces cell cycle arrest and apoptosis. Increased PTHrP expression has been implicated in TGF-β-induced growth inhibition in human hepatocellular carcinoma cells. However, whether PTHrP is involved in TGF-β-induced apoptosis remains unknown. Using Hep3B and HuH-7, two human hepatocellular carcinoma cell lines, the current study examined the hypothesis that TGF-β-induced apoptosis is mediated by the induction of PTHrP expression. We found that (1) TGF-β induces PTHrP mRNA expression, protein expression and secretion in a time-dependent fashion; (2) knockdown of PTHrP gene expression or neutralization of secreted PTHrP isoforms blocks TGF-β-induced apoptosis; and (3) TGF-β-induced PTHrP expression is Smad3-dependent. Thus, we have identified PTHrP as a novel mediator for TGF-β-induced apoptosis in Hep3B cells. Our findings provide further insights into the mechanisms through which TGF-β conveys tumor suppression activity.

Original languageEnglish (US)
Pages (from-to)40-46
Number of pages7
JournalRegulatory Peptides
Volume184
DOIs
StatePublished - Jun 1 2013

Keywords

  • (TGF)-β
  • Apoptosis
  • PTHrP
  • Parathyroid hormone-related protein
  • Real-time quantitative PCR
  • SiRNA
  • Small interfering RNA
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

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