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PTHrP is a novel mediator for TGF-?-induced apoptosis.

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)-? is an important tumor suppressor that induces cell cycle arrest and apoptosis. Increased PTHrP expression has been implicated in TGF-?-induced growth inhibition in human hepatocellular carcinoma cells. However, whether PTHrP is involved in TGF-?-induced apoptosis remains unknown. Using Hep3B and HuH-7, two human hepatocellular carcinoma cell lines, the current study examined the hypothesis that TGF-?-induced apoptosis is mediated by the induction of PTHrP expression. We found that (1) TGF-? 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-?-induced apoptosis; and (3) TGF-?-induced PTHrP expression is Smad3-dependent. Thus, we have identified PTHrP as a novel mediator for TGF-?-induced apoptosis in Hep3B cells. Our findings provide further insights into the mechanisms through which TGF-? conveys tumor suppression activity.

SUBMITTER: Cao Y

PROVIDER: S-EPMC3894735 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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

Cao Yanna Y Zhang Weili W Gao Xuxia X Zhang Guohua G Falzon Miriam M Townsend Courtney M CM Hellmich Mark R MR Ko Tien C TC

Regulatory peptides 20130313

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, t ...[more]

PMID: 23499802

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PTHrP is a novel mediator for TGF-?-induced apoptosis.

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

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