Identification of an exon 3 deletion splice variant androgen receptor mRNA in human breast cancer

Int J Cancer. 1997 Aug 7;72(4):574-80. doi: 10.1002/(sici)1097-0215(19970807)72:4<574::aid-ijc4>3.0.co;2-n.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Base Sequence
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • DNA, Complementary / genetics
  • DNA, Complementary / metabolism
  • Exons*
  • Female
  • Gene Deletion*
  • Humans
  • Mutation
  • Polymerase Chain Reaction
  • RNA Splicing*
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Receptors, Androgen / biosynthesis
  • Receptors, Androgen / genetics*
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • DNA, Complementary
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Androgen