Faculty Collaboration Database

Analog of H2 relaxin exhibits antagonistic properties and impairs prostate tumor growth. FASEB J 2007 Mar;21(3):754-65

Date

01/02/2007

Pubmed ID

17197386

DOI

10.1096/fj.06-6847com

Scopus ID

2-s2.0-33847347702 (requires institutional sign-in at Scopus site)   51 Citations

Abstract

Hormone antagonists can be effective tools to delineate receptor signaling pathways and their resulting downstream physiological actions. Mutation of the receptor binding domain (RBD) of human H2 relaxin (deltaH2) impaired its biological function as measured by cAMP signaling. In a competition assay, deltaH2 exhibited antagonistic activity by blocking recombinant H2 relaxin from binding to receptors on THP-1 cells. In a flow cytometry-based binding assay, deltaH2 demonstrated weak binding to 293T cells expressing the LGR7 receptor in the presence of biotinylated H2 relaxin. When human prostate cancer cell lines (PC-3 and LNCaP) were engineered to overexpress eGFP, wild-type (WT) H2, or deltaH2, and subsequently implanted into NOD/SCID mice, tumor xenografts overexpressing deltaH2 displayed smaller volumes compared to H2 and eGFP controls. Plasma osmolality readings and microvessel density and area assessment suggest that deltaH2 modulates physiological parameters in vivo. In a second murine model, intratumoral injections of lentivectors engineered to express deltaH2/eGFP led to suppressed tumor growth compared to controls. This study provides further evidence supporting a role for H2 relaxin in prostate tumor growth. More importantly, we report how mutation of the H2 relaxin RBD confers the hormone derivative with antagonistic properties, offering a novel reagent for relaxin research.

Author List

Silvertown JD, Symes JC, Neschadim A, Nonaka T, Kao JC, Summerlee AJ, Medin JA

Author

Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line, Tumor
Disease Models, Animal
Humans
Male
Mice
Mice, SCID
Neoplasm Transplantation
Neoplasms, Experimental
Prostatic Neoplasms
Relaxin
Xenograft Model Antitumor Assays