Relaxin promotes prostate cancer progression

Shu Feng, Irina U. Agoulnik, Natalia V. Bogatcheva, Aparna A. Kamat, Bernard Kwabi-Addo, Rile Li, Gustavo Ayala, Michael M. Ittmann, Alexander I. Agoulnik

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Purpose: To understand the role of relaxin peptide inprostate cancer, we analyzed the expression of relaxin and its receptor in human prostate cancer samples, the effects of relaxin signaling on cancer cell phenotype in vitro, and the effects of increased serum relaxin concentrations on cancer progression in vivo. Experimental Design: The relaxin and its receptor leucine-rich repeat containing G protein-coupled receptor 7 (LGR7) expression were studied by quantitative reverse transcription-PCR (11 benign and 44 cancer tissue samples) and by relaxin immunohistochemistry using tissue microarrays containing 10 normal and 69 cancer samples. The effects of relaxin treatment and endogenous relaxin/LGR7 suppression via short interfering RNA in PC-3 and LNCaP cells were analyzed in vitro. The effect of transgenic relaxin overexpression [Tg(Rln1)] on cancer growth and survival was evaluated in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP). Results:The relaxin mRNA expression was significantly higher in recurrent prostate cancer samples. In tissue microarrays of the 10 normal tissues, 8 had lowsta ining in epithelial cells, whereas only 1of 9 high-grade prostatic intraepithelial neoplasia lesions had lowex pression (P = 0.005) and only 29 of 65 cancers had lowexpression (P = 0.047). Stimulation with relaxin increased cell proliferation, invasiveness, and adhesion in vitro. The suppression of relaxin/LGR7 via short interfering RNAs decreased cell invasiveness by 90% to 95% and growth by 10% to 25% and increased cell apoptosis 0.6 to 2.2 times. The Tg(Rln1) TRAMP males had shorter median survival time, associated with the decreased apoptosis of tumor cells, compared with non-Tg(Rln1) TRAMP animals. Conclusions: Relaxin signaling plays a role in prostate cancer progression.

Original languageEnglish (US)
Pages (from-to)1695-1702
Number of pages8
JournalClinical Cancer Research
Volume13
Issue number6
DOIs
StatePublished - Mar 15 2007

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Feng, S., Agoulnik, I. U., Bogatcheva, N. V., Kamat, A. A., Kwabi-Addo, B., Li, R., Ayala, G., Ittmann, M. M., & Agoulnik, A. I. (2007). Relaxin promotes prostate cancer progression. Clinical Cancer Research, 13(6), 1695-1702. https://doi.org/10.1158/1078-0432.CCR-06-2492