Protein kinase A regulatory subunits in colon cancer
Protein kinase A regulatory subunits in colon cancer
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DOI：
10.1038/sj.neo.7900039
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发表时间：
1999-10-01
期刊：
影响因子：
--
通讯作者：
Dransfield, Daniel T.
中科院分区：
文献类型：
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作者：
Carlson, Chris C.;Smithers, Stacy L.;Dransfield, Daniel T.
蛋白激酶A(PKA)根据催化亚基与RI或RII调节亚基的关联性被分为I或II类。这些调节亚基水平和PKA活性本身的变化似乎影响细胞增殖和肿瘤发生。我们检查了45名患者的大肠肿瘤标本，以研究cAMP相关信号分子在调节肿瘤发生中的潜在作用。对人结直肠肿瘤组织匀浆进行蛋白印迹分析(PKA亚单位蛋白水平)和体外蛋白酪氨酸磷酸化分析(PKA催化亚基活性)。RIbeta蛋白水平在升结肠肿瘤中较癌旁粘膜降低200%，在降结肠肿瘤中降低50%。降结肠肿瘤组织中RII蛋白水平较癌旁粘膜下降77%，而升结肠肿瘤组织中RII蛋白表达水平无明显变化。升行和降行肿瘤的PKA活性和催化亚单位蛋白绝对量与癌旁粘膜相比无明显变化。CAMP相关信号分子在结直肠癌组织和正常结直肠组织中存在差异。这些差异不仅可能作为化疗药物的潜在治疗靶点，而且还可能导致识别参与细胞增殖和肿瘤发生的新的调控机制。
The protein kinase A (PKA) is classified as type I or II depending on the association of the catalytic subunit with either the RI or RII regulatory subunits. Alterations in the levels of these regulatory subunits and PKA activity itself appear to affect cellular proliferation and tumorigenesis. We examined colorectal tumor specimens from 45 patients to investigate the potential role of cAMP-related signaling molecules in regulating tumorigenesis. Western blot analysis (PKA subunit protein levels) and in vitro kemptide phosphorylation assays (PKA catalytic subunit activity) were performed on human colorectal tumor tissue homogenates. RIbeta protein levels were decreased 200% in ascending and 50% in descending colonic tumors compared to adjacent mucosa. RII protein levels were decreased 77% in descending colonic tumors but no change was observed in ascending colonic tumors compared to adjacent mucosa. PKA activity and the absolute amount of catalytic subunit protein in ascending and descending tumors were unchanged compared to adjacent mucosa. Differences in cAMP-related signaling molecules exist between neoplastic and normal colorectal tissues. These differences may not only serve as potential therapeutic targets for chemotherapeutic agents, but also lead to the identification of novel regulatory mechanisms involved in cellular proliferation and tumorigenesis.