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  • Title: Identification of an exon 3 deletion splice variant androgen receptor mRNA in human breast cancer.
    Author: Zhu X, Daffada AA, Chan CM, Dowsett M.
    Journal: Int J Cancer; 1997 Aug 07; 72(4):574-80. PubMed ID: 9259393.
    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.
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