Identification of an exon 3 deletion splice variant androgen receptor mRNA in human breast cancer.
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.
Zhu
X
X
Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.
Daffada
A A
AA
Chan
C M
CM
Dowsett
M
M
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
D018076:DNA, Complementary; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011944:Receptors, Androgen