title: 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.
authors.affiliation: Department of Clinical Pharmacology, Flinders Medical Centre, Flinders University School of Medicine, Bedford Park, SA, 5042, Australia, donggui.hu@flinders.edu.au.
authors.forename: Dong Gui
authors.initials: DG
authors.lastname: Hu
authors.forename: Theresa E
authors.initials: TE
authors.lastname: Hickey
authors.forename: Connie
authors.initials: C
authors.lastname: Irvine
authors.forename: Dhilushi Dodampege
authors.initials: DD
authors.lastname: Wijayakumara
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Tilley
authors.forename: Luke A
authors.initials: LA
authors.lastname: Selth
authors.forename: Peter I
authors.initials: PI
authors.lastname: Mackenzie
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D005091:Exons / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics; D012326:RNA Splicing; D011944:Receptors, Androgen / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: C410798:AR protein, human; D020033:Protein Isoforms; D011944:Receptors, Androgen