{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:22:02Z","timestamp":1790400122188,"version":"4.1.0"},"reference-count":45,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R25 CA134283"],"award-info":[{"award-number":["R25 CA134283"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:p> The p21-activated kinase 1 ( PAK1) gene encodes a serine\/threonine kinase that is overexpressed in a subset of human breast carcinomas with poor prognosis. The laboratory rat ( Rattus norvegicus) orthologous gene is located at Mammary carcinoma susceptibility 3 ( Mcs3) QTL on rat chromosome 1. We used quantitative PCR to determine effects of Mcs3 genotype and 7,12-dimethylbenz(a)anthracene (DMBA) exposure on Pak1 expression. There was no effect of Mcs3 genotype; however, there was a 3.5-fold higher Pak1 level in DMBA-exposed mammary glands (MGs) than in unexposed glands ( P &lt; 0.05). Sequence variants in Pak1 exons did not alter amino acid sequence between Mcs3-susceptible and -resistant strains. Protein expression of PAK1\/Pak1 in human breast carcinomas and DMBA-exposed rat mammary glands was detected using immunohistochemistry (IHC). Rat mammary glands from 12-wk-old females unexposed to DMBA were negative for Pak1, whereas 24% of carcinogen-exposed mammary glands from age-matched females stained positive for Pak1. The positive mammary glands exposed to carcinogen had no pathological signs of disease. Human breast carcinomas, used as comparative controls, had a 22% positivity rats. This was consistent with other human breast cancer studies of PAK1 expression. Similar frequencies of human\/rat PAK1\/Pak1 expression in female breast carcinomas and carcinogen-induced rat mammary glands, showing no visible pathogenesis of disease, suggests aberrant PAK1 expression is an early event in development of some breast cancers. Laboratory rats will be a useful experimental organism for comparative studies of Pak1-mediated mechanisms of breast carcinogenesis. Future studies of PAK1 as a diagnostic marker of early breast disease are warranted. <\/jats:p>","DOI":"10.1152\/physiolgenomics.00112.2020","type":"journal-article","created":{"date-parts":[[2020,12,21]],"date-time":"2020-12-21T13:45:24Z","timestamp":1608558324000},"page":"61-68","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Chemical carcinogen-induced rat mammary carcinogenesis is a potential model of p21-activated kinase positive female breast cancer"],"prefix":"10.1152","volume":"53","author":[{"given":"Emily L.","family":"Duderstadt","sequence":"first","affiliation":[{"name":"Department of Biochemistry & Molecular Genetics, University of Louisville School of Medicine, Louisville, Kentucky"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A.","family":"McQuaide","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Genetics, University of Louisville 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