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 Pak1expression. There was no effect of Mcs3genotype; however,there was a 3.5-fold higher Pak1level in DMBA-exposed mammary glands compared to unexposed glands (p<0.05). Sequence variants in Pak1exons did not alter amino acid sequence between Mcs3susceptible 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-week-old females not exposed to DMBA were negative for Pak1, while 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.

中文翻译：

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化学致癌物诱导的大鼠乳腺癌是 p21 活化激酶 (PAK1) 阳性乳腺癌的潜在模型

p21 活化激酶 1(PAK1) 基因编码丝氨酸/苏氨酸激酶，该激酶在预后不良的人类乳腺癌亚群中过度表达。实验室大鼠 (Rattus norvegicus) 直系同源基因位于大鼠 1 号染色体上的乳腺癌易感性 3 (Mcs3) QTL。我们使用定量 PCR 来确定 Mcs3 基因型和 7,12-二甲基苯(a)蒽 (DMBA) 暴露对Pak1 表达。Mcs3基因型没有影响；然而，与未暴露的腺体相比，暴露于 DMBA 的乳腺中 Pak1 水平高出 3.5 倍（p<0.05）。Pak1exons 中的序列变异不会改变 Mcs3 易感和抗性菌株之间的氨基酸序列。使用免疫组织化学 (IHC) 检测人乳腺癌和暴露于 DMBA 的大鼠乳腺中 PAK1/Pak1 的蛋白质表达。未暴露于 DMBA 的 12 周龄雌性大鼠的乳腺中 Pak1 呈阴性，而年龄匹配的雌性中 24% 的致癌物暴露的乳腺中 Pak1 呈阳性。暴露于致癌物的阳性乳腺没有疾病的病理迹象。用作比较对照的人类乳腺癌有 22% 的阳性大鼠。这与其他关于 PAK1 表达的人类乳腺癌研究一致。女性乳腺癌和致癌物诱导的大鼠乳腺中人类/大鼠 PAK1/Pak1 表达的相似频率，没有显示出可见的疾病发病机制，表明异常 PAK1 表达是某些乳腺癌发展的早期事件。实验室大鼠将成为比较研究 Pak1 介导的乳腺癌发生机制的有用实验生物。