Connexin 43 expression is associated with increased malignancy in prostate cancer cell lines and functions to promote migration.

Abstract

Impaired expression of connexins, the gap junction subunits that facilitate direct cell-cell communication, have been implicated in prostate cancer growth. To elucidate the crucial role of connexins in prostate cancer progression, we performed a systematic quantitative RT-PCR screening of connexin expression in four representative prostate cancer cell lines across the spectrum of malignancy. Transcripts of several connexin subunits were detected in all four cell lines, and connexin 43 (Cx43) showed marked elevation at both RNA and protein levels in cells with increased metastatic potential. Analysis of gap-junction-mediated intercellular communication revealed homocellular coupling in PC-3 cells, which had the highest C x 43 expression, with minimal coupling in LNCaP cells where C x 43 expression was very low. Treatment with the gap junction inhibitor carbenoxolone or connexin mimetic peptide ACT-1 did not impair cell growth, suggesting that growth is independent of functional gap junctions. PC-3 cells with C x 43 expression reduced by shRNA showed decreased migration in monolayer wound healing assay, as well as decreased transwell invasion capacities when compared to control cells expressing non-targeting shRNA. These results, together with the correlation between C x 43 expression levels and the metastatic capacity of the cell lines, suggest a role of C x 43 in prostate cancer invasion and metastasis.

• Authors: Ao Zhang, Masahiro Hitomi, Noah Bar-Shain, Zafardjan Dalimov, Leigh Ellis, Kiran K Velpula, Gail C Fraizer, Robert G Gourdie, Justin D Lathia
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 13 Pg. 11640-51 (May 10 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25960544 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Connexin 43
• GJA1 protein, human
• GJA1 protein, mouse
• RNA, Messenger

Topics

• Animals
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Connexin 43 (genetics, metabolism)
• Gap Junctions (metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Mice
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Prostatic Neoplasms (genetics, metabolism, pathology)
• RNA Interference
• RNA, Messenger (metabolism)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• Time Factors
• Transfection