Literature DB >> 15221992

Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen-independent status.

Heng Hong1, Chinghai Kao, Meei-Huey Jeng, John N Eble, Michael O Koch, Thomas A Gardner, Shaobo Zhang, Lang Li, Chong-Xian Pan, Zhiqiang Hu, Gregory T MacLennan, Liang Cheng.   

Abstract

BACKGROUND: Coactivator-associated arginine methyltransferase 1 (CARM1) is a transcriptional coactivator of the androgen receptor (AR). It is involved in the regulation of the biologic functions of the AR. It remains to be determined whether CARM1 is involved in prostatic carcinogenesis.
METHODS: The expression of CARM1 in normal prostate epithelium, high-grade prostatic intraepithelial neoplasia (PIN), and prostate carcinoma tissue was examined in 66 previously untreated patients with prostate carcinomas, as well as 12 patients with hormone-independent prostate carcinoma, using immunohistochemical methods.
RESULTS: Cell staining was observed in the cytoplasm and the nucleus. In 66 patients without previous hormonal treatment, the percentage of cells that stained positively for CARM1 in benign prostate tissue specimens (mean values: cytoplasm, 23%; nucleus, 16%) was statistically significantly less than the percentage of positively stained cells in PIN (mean values: cytoplasm, 56%; nucleus, 30%; P < 0.001) and in prostatic adenocarcinoma specimens (mean values: cytoplasm, 79%; nucleus, 53%; P < 0.001). The difference between adenocarcinoma and PIN also was statistically significant (P < 0.001). The staining intensity for CARM1 was significantly lower in benign prostate tissue specimens compared with PIN and prostatic adenocarcinoma specimens (P < 0.001). In the 12 patients with androgen-independent prostatic adenocarcinoma, the expression of CARM1 was significantly increased when compared with patients without previous hormonal treatment. Expression of CARM1 was not correlated with age, Gleason score sum, pathologic stage, lymph node metastasis, extraprostatic extension, surgical margin status, vascular invasion, or perineural invasion.
CONCLUSIONS: The authors found that overexpression of CARM1 was involved in the development of prostate carcinoma as well as androgen-independent prostate carcinoma. Since CARM1 is functionally different from most other transcriptional coactivators of the AR, it may serve as a new target for the treatment of hormone-independent prostate carcinoma. Copyright 2004 American Cancer Society.

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Year:  2004        PMID: 15221992     DOI: 10.1002/cncr.20327

Source DB:  PubMed          Journal:  Cancer        ISSN: 0008-543X            Impact factor:   6.860


  65 in total

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Journal:  Genes Dev       Date:  2011-06-01       Impact factor: 11.361

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Authors:  Karen B O'Brien; Meritxell Alberich-Jordà; Neelu Yadav; Olivier Kocher; Annalisa Diruscio; Alexander Ebralidze; Elena Levantini; Natasha J L Sng; Manoj Bhasin; Tyler Caron; Daehoon Kim; Ulrich Steidl; Gang Huang; Balázs Halmos; Scott J Rodig; Mark T Bedford; Daniel G Tenen; Susumu Kobayashi
Journal:  Development       Date:  2010-07       Impact factor: 6.868

Review 3.  Chemical and biochemical approaches in the study of histone methylation and demethylation.

Authors:  Keqin Kathy Li; Cheng Luo; Dongxia Wang; Hualiang Jiang; Y George Zheng
Journal:  Med Res Rev       Date:  2012-07       Impact factor: 12.944

4.  Design and synthesis of selective, small molecule inhibitors of coactivator-associated arginine methyltransferase 1 (CARM1).

Authors:  H Ü Kaniskan; M S Eram; J Liu; D Smil; M L Martini; Y Shen; V Santhakumar; P J Brown; C Arrowsmith; M Vedadi; J Jin
Journal:  Medchemcomm       Date:  2016-07-13       Impact factor: 3.597

Review 5.  Protein methyltransferases as a target class for drug discovery.

Authors:  Robert A Copeland; Michael E Solomon; Victoria M Richon
Journal:  Nat Rev Drug Discov       Date:  2009-09       Impact factor: 84.694

Review 6.  Chemical biology of protein arginine modifications in epigenetic regulation.

Authors:  Jakob Fuhrmann; Kathleen W Clancy; Paul R Thompson
Journal:  Chem Rev       Date:  2015-05-13       Impact factor: 60.622

Review 7.  Inhibitors of Protein Methyltransferases and Demethylases.

Authors:  H Ümit Kaniskan; Michael L Martini; Jian Jin
Journal:  Chem Rev       Date:  2017-03-24       Impact factor: 60.622

8.  Identification of small-molecule enhancers of arginine methylation catalyzed by coactivator-associated arginine methyltransferase 1.

Authors:  Sabrina Castellano; Astrid Spannhoff; Ciro Milite; Fabrizio Dal Piaz; Donghang Cheng; Alessandra Tosco; Monica Viviano; Abdellah Yamani; Agostino Cianciulli; Marina Sala; Vincent Cura; Jean Cavarelli; Ettore Novellino; Antonello Mai; Mark T Bedford; Gianluca Sbardella
Journal:  J Med Chem       Date:  2012-11-02       Impact factor: 7.446

9.  Differential CARM1 expression in prostate and colorectal cancers.

Authors:  Young-Rang Kim; Byung Kook Lee; Ra-Young Park; Nguyen Thi Xuan Nguyen; Jeong A Bae; Dong Deuk Kwon; Chaeyong Jung
Journal:  BMC Cancer       Date:  2010-05-13       Impact factor: 4.430

Review 10.  Chromatin-modifying enzymes as therapeutic targets--Part 1.

Authors:  Brian R Keppler; Trevor K Archer
Journal:  Expert Opin Ther Targets       Date:  2008-10       Impact factor: 6.902

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