c-Jun NH(2)-terminal kinase mediates leptin-stimulated androgen-independent prostate cancer cell proliferation via signal transducer and activator of transcription 3 and Akt

Biochimica Et Biophysica Acta
Toshiaki MiyazakiYoshiki Iwamoto

Abstract

Obesity is associated with advanced prostate cancer. Here we demonstrate that in mouse prostate cancer TRAMP-C1 cells epididymal fat extracts from high-fat diet-fed obese mice stimulate androgen-independent cell growth more significantly than those from low-fat diet-fed lean mice or genetically obese leptin-deficient ob/ob mice in correlation with leptin concentrations. This result suggests that obesity promotes androgen-independent prostate cancer cell growth via adipose leptin. We have reported that added leptin stimulates androgen-independent prostate cancer cell proliferation through c-Jun NH(2)-terminal kinase (JNK). As with JNK, signal transducer and activator of transcription 3 (STAT3) and Akt are implicated in androgen-independent prostate cancer. In this study, we identify novel interaction of these three molecules in leptin-stimulated androgen-independent cell proliferation. Leptin activates JNK, STAT3 and Akt in a biphasic manner with a similar time-course. Pharmacological JNK inhibition suppresses leptin-stimulated DNA binding activity, as well as Ser-727 phosphorylation, of STAT3. Since JNK upregulates STAT3 activity via Ser-727 phosphorylation, JNK mediates leptin-stimulated STAT3 activation through Ser-727 phosph...Continue Reading

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Citations

Jun 15, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jia LiuFei Chen
Nov 26, 2015·International Journal of Molecular Sciences·Pei-Sung HsuWei-Ning Lin
May 5, 2011·The Prostate·Sigal Samuel-MendelsohnRonnie J Barkey
Jun 21, 2014·Expert Opinion on Therapeutic Targets·Weiqiang ZhouChengyu Luo
Aug 27, 2016·Advanced Biomedical Research·Fatemehsadat AmjadiShaghayegh Haghjooy Javanmard
May 25, 2011·World Journal of Stem Cells·Yan ZhangMikhail G Kolonin
Apr 12, 2013·Experimental Biology and Medicine·Linglin Xie, Weiqun Wang
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Dec 15, 2012·Cancer Science·Ryota TakahashiKazuhiko Koike
Apr 15, 2014·Annals of the New York Academy of Sciences·Nathan A Berger
Aug 13, 2009·Molecular Cancer Research : MCR·Anas SaadeddinAbdolrahman Shams Nateri
Sep 4, 2021·European Journal of Pharmacology·Vipasha GautamLekha Saha
Feb 1, 2012·Biochimica Et Biophysica Acta·Shanchun GuoRuben R Gonzalez-Perez

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