Expression of Pleiotrophin in the Prostate is Androgen Regulated and it Functions as an Autocrine Regulator of Mesenchyme and Cancer Associated Fibroblasts and as a Paracrine Regulator of Epithelia

نویسندگان

  • Brigid Orr
  • Griet Vanpoucke
  • O Cathal Grace
  • Lee Smith
  • Richard A Anderson
  • Antony CP Riddick
  • Omar E Franco
  • Simon W Hayward
  • Axel A Thomson
چکیده

BACKGROUND Androgens and paracrine signaling from mesenchyme/stroma regulate development and disease of the prostate, and gene profiling studies of inductive prostate mesenchyme have identified candidate molecules such as pleiotrophin (Ptn). METHODS Ptn transcripts and protein were localized by in situ and immunohistochemistry and Ptn mRNA was quantitated by Northern blot and qRT-PCR. Ptn function was examined by addition of hPTN protein to rat ventral prostate organ cultures, primary human fetal prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. RESULTS During development, Ptn transcripts and protein were expressed in ventral mesenchymal pad (VMP) and prostatic mesenchyme. Ptn was localized to mesenchyme surrounding ductal epithelial tips undergoing branching morphogenesis, and was located on the surface of epithelia. hPTN protein stimulated branching morphogenesis and stromal and epithelial proliferation, when added to rat VP cultures, and also stimulated growth of fetal human prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. PTN mRNA was enriched in patient-matched normal prostate fibroblasts versus prostate cancer associated fibroblasts. PTN also showed male enriched expression in fetal human male urethra versus female, and between wt male and ARKO male mice. Transcripts for PTN were upregulated by testosterone in fetal human prostate fibroblasts and organ cultures of female rat VMP. Ptn protein was increased by testosterone in organ cultures of female rat VMP and in rat male urethra compared to female. CONCLUSIONS Our data suggest that in the prostate Ptn functions as a regulator of both mesenchymal and epithelial proliferation, and that androgens regulate Ptn levels.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Role of Ghrelin in Cancer

Cancer is one of the most fatal diseases in human beings which annually leads to death of 30000 individuals in Iran. Prevention, diagnosis and treatment of cancer is one of the major scientific challenges all around the world. It seems that increased incidence of several cancers such as colon and prostate and their mortality are connected with obesity. It is suggested that obesity and metabolic...

متن کامل

Down regulation of GTPase regulator associated with the focal adhesion kinase (GRAF) gene expression in patients with acute myeloblastic leukemia

Introduction: GTPase regulator associated with focal adhesion kinase (GRAF) is a recently identified GTPase activating protein that has the tumor suppressor properties. However, the expression level of GRAF in leukemia had received less attention. The main purpose of this research was the evaluating of the expression level of GRAF in patients with acute myeloid leukemia (AML). Materials and met...

متن کامل

The Role of Adiponectin in Prostate Cancer: A Narrative Review

Prostate cancer (PCa) is the most common type of cancer among men over 60 years old. The aggressiveness and mortality of PCa can be correlated with obesity. Adipose tissue-derived cytokines such as adiponectin may explain the correlation between PCa and obesity. Since the correlation between adiponectin and aggressive PCa is still not fully evaluated, we aimed to investigate the probable role o...

متن کامل

Therapeutic Efficacy Analysis of lncRNA NEAT1 Gene Knockout and Apoptosis Induction in Prostate Cancer Cell Line Using CRISPR/Cas9

Background and Objective: Long non-coding ribonucleic acid (lncRNA) has been identified as an important gene regulator and prognostic marker in various cancers. The present study aimed to investigate the effects of Nuclear Paraspeckle Assembly Transcript1 (NEAT1) gene knockout using Clustered Regularly Interspaced Short Palindromic Repeats-associated Protein 9 (CRISPR/Cas9) in PC-3 cell line. ...

متن کامل

Resistin and Visfatin Expression in HCT-116 Colorectal Cancer Cell Line

Adipocytokines, hormones secreted from adipose tissue, have been shown to be associated with many cancers such as breast, prostate and colorectal cancer. Recent studies have indicated that resistin and visfatin, two of these adipokines have high level plasma concentrations in colorectal cancer patients and may be promising biomarkers for colorectal cancer. The aim of this study was to identify ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 71  شماره 

صفحات  -

تاریخ انتشار 2011