Protein arginine methyltransferase 10 is required for androgen-dependent proliferation of LNCaP prostate cancer cells

Abstract

Androgen receptor (AR) signaling is the master regulator of prostate cell growth. Here, to better understand AR signaling, we searched for AR-interacting proteins by yeast two-hybrid screening and identified protein arginine methyltransferase 10 (PRMT10) as one of the interacting proteins. PRMT10 was highly expressed in reproductive tissues, such as prostate. Immunostaining showed that PRMT10 was expressed in the nucleus of both epithelia and stroma of rat prostate. In human prostate cancer LNCaP cells, PRMT10 co-immunoprecipitated with AR in both the presence and absence of dihydrotestosterone (DHT). Knockdown of PRMT10 by siRNA decreased DHT-dependent LNCaP cell growth and induction of prostate-specific antigen, an AR-target gene, without apparent loss of AR. DHT decreased PRMT10 at both the mRNA and protein levels. The decrease in PRMT10 was canceled by knockdown of AR or an AR antagonist. These results indicate that PRMT10 plays an important role in androgen-dependent proliferation of prostate cancer cells.

Role of androgens in energy metabolism affecting on body composition, metabolic syndrome, type 2 diabetes, cardiovascular disease, and longevity: lessons from a meta-analysis and rodent studies

“…The ligand-activated AR binds to the androgen response element within target gene promoters [85] and thus stimulates the transcription of target genes. Coactivators and corepressors are essential for the modulation of AR transactivation [86][87][88][89][90][91]. Exon 1 in the AR gene contains polymorphic CAG and GGN trinucleotide repeats, which affect the transcriptional activity of the AR [92].…”

Identification of a novel K311 ubiquitination site critical for androgen receptor transcriptional activity

“…Mutating K311 also caused a significant increase in the drug metabolism pathway. Androgen receptor activity has previously been linked to arginine metabolism with AR interacting with protein arginine methyltransferase 10 (PRMT10) (31), similarly PRTM6 was reported to co-activate the AR (32), conversely AR deficiency alters the arginine-vasopressin sexually dimorphic system (33). …”

Protein Arginine Methyltransferase 6 Involved in Germ Cell Viability during Spermatogenesis and Down-Regulated by the Androgen Receptor

“…It was reported that PRMT2, one of the protein arginine methyltransferase family members, was recruited by and acted as a coactivator of AR in the presence of androgens [ 10 ]. Protein arginine methyltransferase 10 was also down regulated by AR [ 11 ]. Research also showed that PRMT6 could methylate and interact with AR, and that the interaction between them was obviously enhanced when AR was mutant [ 12 ].…”