Identification of androgen receptor splice variant transcripts in breast cancer cell lines and human tissues.

Abstract

The androgen receptor (AR) is widely expressed in human tissues and has biological function in many male and female organs. In particular, the AR plays a critical role in the biology and pathology of the prostate gland. AR activity inhibits breast growth and has pleiotropic actions in breast cancer that are subtype-dependent. Expression of AR splice variants (ARVs) and their role in prostate carcinogenesis has been elucidated in recent studies. We hypothesised that ARVs are also expressed in breast cancers and other hormone sensitive tissues. Herein, the expression of five previously identified ARV transcripts with documented transcriptional capacity (AR-V1, -V3, -V4, -V7, and -V9) was examined in 6 breast (MFM223, MDA-MB-453, MDA-MB-231, ZR75.1, MCF-7, T47D), two prostate (VCaP, LNCaP), and one liver (HepG2) cancer cell lines, a human embryonic kidney cell line (HEK293), and a panel of RNAs representing 21 different human tissues. Four ARVs (V1, V3, V7, V9) were detected to some degree in almost all cell lines and tissues. In addition, four novel ARVs containing a cryptic exon 9 (CE9) were detected in MDA-MB-453 and VCaP cells. Sequencing of ARV amplicons revealed a single nucleotide substitution within CE3 in lung and placental tissue samples that could be translated as an Ile (ATT)>Val (GTT) substitution in the AR-V7 variant protein. Collectively, these data provides insight into the potential complexity of AR transcriptional splicing events in breast cancer cell lines and diverse human tissues, thereby establishing a rationale for further exploration of ARVs in breast cancer and other human pathologies.