title: PTHrP is a novel mediator for TGF-β-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)-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.
authors.affiliation: Department of Surgery, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Yanna
authors.initials: Y
authors.lastname: Cao
authors.forename: Weili
authors.initials: W
authors.lastname: Zhang
authors.forename: Xuxia
authors.initials: X
authors.lastname: Gao
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhang
authors.forename: Miriam
authors.initials: M
authors.lastname: Falzon
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Townsend
authors.forename: Mark R
authors.initials: MR
authors.lastname: Hellmich
authors.forename: Tien C
authors.initials: TC
authors.lastname: Ko
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta