CAMP BINDING PROTEINS IN MAMMARY CANCER GROWTH CONTROL

CAMP 结合蛋白在乳腺癌生长控制中的作用

• 批准号: 3962974
• 负责人: Y S CHO-CHUNG
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3962974
• 关键词: affinity chromatography; breast neoplasms; cell free system; cell growth regulation; chemical binding; cyclic AMP; gel electrophoresis; hormone related neoplasm /cancer; human tissue; molecular oncology; molecular site; morphology; mouse mammary tumor virus; neoplasm /cancer therapy; neoplastic growth; prognosis; tissue /cell culture

Cyclic AMP (cAMP) in mammalian cells functions by binding to cAMP receptor protein, the regulatory subunit of cAMP-dependent protein kinase. The cAMP receptor protein has two different cAMP binding sites, and cAMP analogs that specifically bind to either one of the two binding sites are known as Site 1-selective (C-2 and C-8 analogs) and Site 2-selective (C-6 analogs), respectively. Further the Site 1- and Site 2-selective analogs in combination produce synergistic enhancement of the binding to cAMp receptor protein and protein kinase activation in vitro. Application of these in vitro findings to demonstrate cAMP analog-mediated response in vivo, in intact cells or tissues has been scarce. Moreover, virtually all past studies of cAMP-regulation of cell growth employed a few, early known, cAMP analogs which are weakly active for protein kinase and effective only at unphysiological high mM concentrations. The site-selective cAMP analogs which are many-fold more active for protein kinase have never been tested for their growth regulatory effect. We, therefore, investigated the effect of site-selective cAMP analogs on the growth and morphology of several breast and colon human cancer cell lines and the in vivo growth of rodent mammary tumors. The analog effect on the cell growth will be correlated with the response of cAMP receptor protein present in the cancer cells. The goal of this study is to elucidate the growth regulatory mechanism of cAMP analogs which can be extrapolated to the treatment of human cancer.

哺乳动物细胞中的环磷酸腺苷（cAMP）通过与cAMP受体结合发挥作用 蛋白，cAMP依赖性蛋白激酶的调节亚基。 营地 受体蛋白具有两个不同的cAMP结合位点，cAMP类似物 特异性结合两个结合位点中的任何一个的分子被称为 位点1选择性（C-2和C-8类似物）和位点2选择性（C-6类似物）， 分别 此外，还可以将在本发明中的位点1-和位点2-选择性类似物 组合产生与cAMp受体结合的协同增强 体外蛋白和蛋白激酶活化。 应用这些体外研究结果证明cAMP类似物介导的 在体内，在完整的细胞或组织中的反应已经很少。 此外，委员会认为， 几乎所有过去关于cAMP调节细胞生长的研究都采用了 少数早期已知的cAMP类似物对蛋白激酶活性弱 并且仅在非生理高mM浓度下有效。 的 对蛋白质活性高许多倍位点选择性cAMP类似物 激酶从未被测试过它们的生长调节作用。 因此，我们研究了位点选择性cAMP类似物对 几种乳腺癌和结肠癌细胞生长和形态学观察 线和啮齿动物乳腺肿瘤的体内生长。 类比效应 对细胞生长的影响与cAMP受体的反应有关 癌细胞中的蛋白质。 本研究的目的是 阐明cAMP类似物的生长调节机制， 用于治疗人类癌症。