Relaxin promotes prostate cancer progression.
OBJECTIVE
To understand the role of relaxin peptide in prostate 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.


METHODS
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 low staining in epithelial cells, whereas only 1 of 9 high-grade prostatic intraepithelial neoplasia lesions had low expression (P = 0.005) and only 29 of 65 cancers had low expression (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.
Feng
Shu
S
Department of Obstetrics and Gynecology, Molecular and Cellular Biology, and Pathology, Baylor College of Medicine, Houston, TX 77030, USA.
Agoulnik
Irina U
IU
Bogatcheva
Natalia V
NV
Kamat
Aparna A
AA
Kwabi-Addo
Bernard
B
Li
Rile
R
Ayala
Gustavo
G
Ittmann
Michael M
MM
Agoulnik
Alexander I
AI
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018000:Receptors, Peptide; D012065:Relaxin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D016019:Survival Analysis
D008565:Membrane Proteins; C095067:RLN1 protein, human; C417543:RXFP1 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D012065:Relaxin