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Androgen Regulation of CXCR4/CXCR7 Chemokine Receptors: Disconnect between Transcription and Translation in Androgen‐responsive Prostate Cancer LNCaP Cells
Author(s) -
Yu Lu,
Yu Liangli,
Wang Thomas
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.629.9
Subject(s) - lncap , du145 , androgen receptor , dihydrotestosterone , chemokine , cxcr4 , prostate cancer , androgen , medicine , cancer research , endocrinology , biology , chemistry , receptor , cancer , hormone
Chemokines and sex hormones are involved in prostate cancer (PCa) development. CXC‐motif ligand 12 (CXCL12) and its G‐protein‐coupled seven‐span transmembrane receptors (chemokine CXC‐motif receptor 4 and 7) are the primary regulators for PCa cell migration, invasion, and expression of metalloproteinase. The relationship between androgen and this pathway is less clear. Using real‐time PCR, we found that the androgen‐responsive LNCaP cell line had higher mRNA levels of CXCL12 and CXCR7 when compared to androgen‐unresponsive PCa cell lines such as DU145 and PC‐3. CXCR4 expression was DU145 > LNCaP > PC3. DHT (1nM) treatment of LNCaP cells for 48h inhibited CXCR7 mRNA expression by 70.70%. Moreover, the expression of CXCR4 mRNA level in LNCaP cells increased 6.29‐fold by DHT treatment. The effect of DHT on CXCR4 and CXCR7 in LNCaP cells followed a dose‐ and time‐ dependent manner at the transcriptional level. Silence of androgen receptor using siRNA significantly attenuated the effects of DHT on CXCR7 and CXCR4 mRNA by 61.32% and 72.51%, respectively. However, at protein level only a small decrease (26.75%) in CXCR7 protein level by DHT was detected using western blot. There were no significant changes found for CXCR4. In summary, DHT significantly increased CXCR4 and decreased CXCR7 at mRNA level. Effect of DHT on CXCR4 and 7 at translational level was minimal. Our study indicated that there appeared to be disconnect of the effect of DHT on CXCL12/CXCR4/CXCR7 chemokine axis between transcriptional and translation machinery in androgen‐responsive LNCaP cell line.