PMID- 14968437 OWN - NLM STAT- MEDLINE DCOM- 20040330 LR - 20071114 IS - 0270-4137 (Print) IS - 0270-4137 (Linking) VI - 58 IP - 4 DP - 2004 Mar 1 TI - Effects of transforming growth factor-beta1 on parathyroid hormone-related protein mRNA expression and protein secretion in canine prostate epithelial, stromal, and carcinoma cells. PG - 366-73 AB - BACKGROUND: Bone metastases of prostate carcinoma are associated with osteoblastic metastases. Tumor-derived factors, such as parathyroid hormone-related protein (PTHrP), may promote the development of osteoblastic metastases. We examined the effect of transforming growth factor-beta1 (TGF beta 1) on PTHrP mRNA expression and PTHrP secretion in normal canine prostate epithelial cells (PEC) and stromal cells (PSC), and in canine prostate carcinoma cells (PCC). METHODS: Primary cultures of PEC, PSC, and PCC were produced. The effect of TGF beta 1 on PTHrP mRNA expression was measured by Northern blot, and secretion of PTHrP into culture medium was measured by immunoradiometric assay (IRMA). Degradation of recombinant-human PTHrP (rhPTHrP) (1-84) inoculated in prostate cell cultures was measured over 24 hr. Arginine esterase (AE) activity in tissue and conditioned medium was also measured. RESULTS: TGF beta 1 increased PTHrP mRNA expression in a time- and dose-dependent manner in PEC and in PCC. TGF beta 1 decreased PTHrP mRNA in PSC. TGF beta 1 significantly increased PTHrP secretion (P < or = 0.05) into PEC but not PSC conditioned medium. rhPTHrP was significantly (P < or = 0.05) degraded in PEC conditioned medium as compared to PSC conditioned medium. AE activity was present in prostate and prostate carcinoma tissue, but not in conditioned medium from PEC or PSC. CONCLUSIONS: TGF beta 1 increased PTHrP mRNA expression in canine PEC and PCC, and decreased expression in PSC. This regulatory pathway may be important in the pathogenesis of osteoblastic metastases. CI - Copyright 2004 Wiley-Liss, Inc. FAU - Sellers, Rani S AU - Sellers RS AD - The Department of Veterinary Biosciences, The Ohio State University, Columbus, 43210, USA. FAU - LeRoy, Bruce E AU - LeRoy BE FAU - Blomme, Eric A G AU - Blomme EA FAU - Tannehill-Gregg, Sarah AU - Tannehill-Gregg S FAU - Corn, Stephanie AU - Corn S FAU - Rosol, Thomas J AU - Rosol TJ LA - eng GR - CA-09338/CA/NCI NIH HHS/United States GR - CA-77911/CA/NCI NIH HHS/United States GR - CA79110-01/CA/NCI NIH HHS/United States GR - RR-00168/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Prostate JT - The Prostate JID - 8101368 RN - 0 (Parathyroid Hormone-Related Protein) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Animals MH - Dogs MH - Epithelial Cells/cytology/drug effects/pathology/physiology MH - Gene Expression Regulation/*drug effects MH - Male MH - Parathyroid Hormone-Related Protein/*genetics MH - Prostate/cytology/*physiology MH - Prostatic Neoplasms/genetics/pathology/*physiopathology MH - RNA, Messenger/*genetics MH - Stromal Cells/*cytology/drug effects/pathology/physiology MH - Transforming Growth Factor beta/*pharmacology EDAT- 2004/02/18 05:00 MHDA- 2004/03/31 05:00 CRDT- 2004/02/18 05:00 PHST- 2004/02/18 05:00 [pubmed] PHST- 2004/03/31 05:00 [medline] PHST- 2004/02/18 05:00 [entrez] AID - 10.1002/pros.20029 [doi] PST - ppublish SO - Prostate. 2004 Mar 1;58(4):366-73. doi: 10.1002/pros.20029.