title: Identification of an exon 3 deletion splice variant androgen receptor mRNA in human breast cancer.
abstract: Androgens and androgen receptor (AR) are involved in many regulatory processes in the growth of female breast cells. Mutations in the AR gene and/or alterations of the AR protein sequence may be related to the development and progression of breast cancer. Using reverse transcription-polymerase chain reaction we have examined 31 female breast-cancer samples, 5 normal female breast tissues and 6 breast-cancer cell lines for the presence of splice variants of AR mRNA and have identified an exon 3 deletion splice variant (delta3AR). The higher expression of the variant relative to the wild-type AR (WT AR) was found in 7 breast-cancer samples (delta3/WT > 15%) and relatively lower levels of the variant were observed in 3 breast-cancer cell lines (delta3/WT < 5%). However, in normal breast tissues, expression of the variant was undetectable by Southern blot analysis. In vitro translation of the delta3AR mRNA resulted in a variant AR protein of about 105 kDa, smaller than the WT AR by about 5 kDa. We thus report an exon deletion splice variant of AR mRNA in breast cancer. The variant protein is predicted to lack the second zinc finger within the DNA-binding domain and is expected to be unable or to have reduced ability to bind to androgen-response elements and to activate transcription. The relatively high expression of this AR variant in some breast-cancer tissues may indicate its role in regulating the growth of these cancers.
authors.affiliation: Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: A A
authors.initials: AA
authors.lastname: Daffada
authors.forename: C M
authors.initials: CM
authors.lastname: Chan
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011944:Receptors, Androgen