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dc.contributor.authorTilley, W.en
dc.contributor.authorBuchanan, G.en
dc.contributor.authorHickey, T.en
dc.contributor.authorBentel, J.en
dc.identifier.citationClinical Cancer Research, 1996; 2(2):277-285en
dc.description.abstractProgression to androgen-independent growth of human prostate cancers may be mediated by alterations in the structure and/or expression of the androgen receptor (AR) gene. To date, mutations in the AR gene have largely been identified in hormone refractory tumors. In this study, sin- gle-strand conformational polymorphism analysis and DNA sequencing of the entire AR gene coding region was per- formed on 25 primary prostate tumors sampled prior to initiation of hormonal (i.e., androgen ablation) therapy. Base changes leading to amino acid substitutions in the AR were identified in 11 (44%) tumors. The presence of AR amino acid substitutions was associated with decreased im- munohistochemical staining for AR in tumor cells and the rapid failure of subsequent hormonal therapies. Single- strand conformational polymorphism analysis of exons 2, 3, and 8 of the X-linked hypoxanthine guanine phosphoribosyl transferase (HPRT) gene in the same samples revealed no bandshifts, suggesting that the high frequency of AR gene mutations detected was not a consequence of generalized genetic instability. These data indicate that AR gene muta- tions occur commonly in advanced prostate cancers prior to endocrine treatment of disease and may contribute to al- tered androgen responsiveness of the tumors.en
dc.description.statementofresponsibilityWayne D. Tilley, Grant Buchanan, Theresa E. Hickey and Jacqueline M. Bentelen
dc.publisherAmerican Association for Cancer Researchen
dc.rights© 1996, American Association for Cancer Researchen
dc.subjectTumor Cells, Cultured; Humans; Prostatic Neoplasms; Prostatic Hyperplasia; Hypoxanthine Phosphoribosyltransferase; Receptors, Androgen; DNA; Androgens; Immunohistochemistry; Polymerase Chain Reaction; Repetitive Sequences, Nucleic Acid; Mutation; Polymorphism, Single-Stranded Conformational; Maleen
dc.titleMutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independenceen
dc.typeJournal articleen
pubs.library.collectionMedicine publicationsen
dc.identifier.orcidTilley, W. [0000-0003-1893-2626]en
dc.identifier.orcidHickey, T. [0000-0002-2752-730X]en
Appears in Collections:Medicine publications

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