{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:19:52Z","timestamp":1791404392750,"version":"4.3.3"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,2,7]],"date-time":"2015-02-07T00:00:00Z","timestamp":1423267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000947","name":"Australian Cancer Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000947","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001169","name":"Cancer Council Tasmania","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001169","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012503","name":"Royal Hobart Hospital Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012503","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100015796","name":"Tasmanian Community Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015796","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Max Bruce Trust"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Integrin alpha2 beta1 (\u03b1<jats:sub>2<\/jats:sub>\u03b2<jats:sub>1<\/jats:sub>) plays an integral role in tumour cell invasion, metastasis and angiogenesis, and altered expression of the receptor has been linked to tumour prognosis in several solid tumours. However, the relationship is complex, with both increased and decreased expression associated with different stages of tumour metastases in several tumour types. The <jats:italic>ITGA2<\/jats:italic> gene, which codes for the \u03b1<jats:sub>2<\/jats:sub> subunit, was examined to investigate whether a large CpG island associated with its promoter region is involved in the differential expression of <jats:italic>ITGA2<\/jats:italic> observed in prostate cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Bisulphite sequencing of the <jats:italic>ITGA2<\/jats:italic> promoter was used to assess methylation in formalin\u2010fixed paraffin\u2010embedded (FFPE) prostate tumour specimens and prostate cancer cell lines, PC3, 22Rv1 and LNCaP. Changes in <jats:italic>ITGA2<\/jats:italic> mRNA expression were measured using quantitative PCR. <jats:italic>ITGA2<\/jats:italic> functionality was interrogated using cell migration scratch assays and siRNA knockdown experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Bisulphite sequencing revealed strikingly decreased methylation at key CpG sites within the promoter of tumour samples, when compared with normal prostate tissue. Altered methylation of this CpG island is also associated with differences in expression in the non\u2010invasive LNCaP, and the highly metastatic PC3 and 22Rv1 prostate cancer cell lines. Further bisulphite sequencing confirmed that selected CpGs were highly methylated in LNCaP cells, whilst only low levels of methylation were observed in PC3 and 22Rv1 cells, correlating with <jats:italic>ITGA2<\/jats:italic>  transcript levels. Examination of the increased expression of <jats:italic>ITGA2<\/jats:italic> was shown to influence migratory potential via scratch assay in PC3, 22Rv1 and LNCaP cells, and was confirmed by siRNA knockdown experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Taken together, our data supports the assertion that epigenetic modification of the <jats:italic>ITGA2<\/jats:italic> promoter is a mechanism by which <jats:italic>ITGA2<\/jats:italic> expression is regulated. <jats:italic>Prostate 75:723\u2013734, 2015<\/jats:italic>. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.22954","type":"journal-article","created":{"date-parts":[[2015,2,7]],"date-time":"2015-02-07T16:17:00Z","timestamp":1423325820000},"page":"723-734","source":"Crossref","is-referenced-by-count":29,"title":["Regulation of the <i>ITGA2<\/i> gene by epigenetic mechanisms in prostate cancer"],"prefix":"10.1002","volume":"75","author":[{"given":"Suyin 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