title: Interleukin-17 promotes formation and growth of prostate adenocarcinoma in mouse models.
abstract: The contributions of interleukin (IL)-17 to cancer remain unclear and somewhat controversial. We took a genetic approach to explore its role in prostate cancers by interbreeding IL-17 receptor C (IL-17RC)-deficient mice with mice that are conditionally mutant for PTEN, one established preclinical model for prostate cancer. Mice that were IL-17RC-deficient (IL-17RC(-)) displayed prostates that were smaller than mice that maintained IL-17RC expression (IL-17RC(+)). In addition, IL-17RC(-) mice developed a reduced number of invasive prostate adenocarcinomas with lower rates of cellular proliferation and higher apoptosis than IL-17RC(+) mice. Moreover, the fibromuscular stroma surrounding prostatic glands was relatively thicker in IL-17RC(-) mice and was associated with decreased matrix metalloproteinase (Mmp)7 expression and increased Timp1, 2, and 4 expression, whereas administration of recombinant mouse IL-17 induced prostatic expression of Mmp7. Taken together, our results suggested that IL-17 promotes the formation and growth of prostate adenocarcinoma, and that an IL-17-MMP7 signaling axis is required for the transition of prostatic intraepithelial neoplasia to frank adenocarcinoma.
authors.affiliation: Department of Structural & Cellular Biology, School of Medicine, New Orleans, LA, USA.
authors.forename: Qiuyang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Sen
authors.initials: S
authors.lastname: Liu
authors.forename: Dongxia
authors.initials: D
authors.lastname: Ge
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Xue
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Xiong
authors.forename: Asim B
authors.initials: AB
authors.lastname: Abdel-Mageed
authors.forename: Leann
authors.initials: L
authors.lastname: Myers
authors.forename: Steven M
authors.initials: SM
authors.lastname: Hill
authors.forename: Brian G
authors.initials: BG
authors.lastname: Rowan
authors.forename: Oliver
authors.initials: O
authors.lastname: Sartor
authors.forename: Jonathan
authors.initials: J
authors.lastname: Melamed
authors.forename: Zhenbang
authors.initials: Z
authors.lastname: Chen
authors.forename: Zongbing
authors.initials: Z
authors.lastname: You
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D020381:Interleukin-17 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000235:genetics; D011467:Prostate / Q000276:immunology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism*; D053722:Receptors, Interleukin-17 / Q000235:genetics
chemical_list: C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse