Differential coupling of the PAC1 SV1 splice variant on human colonic tumors to the activation of intracellular cAMP but not intracellular Ca2+ does not activate tumor proliferation
Differential coupling of the PAC1 SV1 splice variant on human colonic tumors to the activation of intracellular cAMP but not intracellular Ca2+ does not activate tumor proliferation
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DOI：
10.1385/jmn:22:1-2:83
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发表时间：
2004-01-01
影响因子：
3.1
通讯作者：
Pisegna, JR
中科院分区：
文献类型：
--
作者：
Germano, PM;Le, SV;Pisegna, JR
PAC 1是最近克隆和表征的七螺旋G蛋白偶联受体，其对PACAP-27和PACAP-38具有高亲和力，并且差异偶联以激活细胞内Call和cAMP。PAC 1表达为四种主要的剪接变体，每种变体具有与肌醇磷酸和细胞内Ca 2+的差异偶联。PAC 1以前已被证明表达和调节非鳞状细胞肺癌细胞以及乳腺癌细胞系的生长和增殖。PAC 1在HCT 8人结肠癌细胞系上表达，并与细胞内cAMP和Ca 2+的活化偶联，从而刺激生长。在目前的研究中，我们对比了垂体腺苷酸环化酶激活多肽（PACAP）对HCT 8结肠癌细胞系的HCT 116和FET细胞系的影响，其中PAC 1表达为SV 1或HIP剪接变体，并且仅与cAMP的激活偶联，而不与细胞内Ca 2+的激活偶联。这些数据表明，人结肠肿瘤细胞表达PAC 1，并与细胞内信号转导分子差异偶联。激活cAMP和Ca 2+的能力似乎是激活肿瘤增殖的先决条件，表明PACAP如何增强某些肿瘤生长的潜在重要因素。
PAC1 is a recently cloned and characterized heptahelical, G protein-coupled receptor with high affinity to PACAP-27 and PACAP-38 and is differentially coupled to activate intracellular Call and cAMP. PAC1 is expressed as four major splice variants, each possessing differential coupling to inositol phosphates and intracellular Ca2+. PAC1 has been shown previously to be expressed and regulate the growth and proliferation of nonsquamous cell lung cancer cells, as well as breast cancer cell lines. PAC1 is expressed on the HCT8 human colon cancer cell line and is coupled to the activation of both intracellular cAMP and Ca2+ with consequent stimulation of growth. In the current study, we contrast the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on the HCT8 colon cancer cell lines to the HCT116 and FET cell lines wherein PAC1 is expressed as the SV1 or HIP splice variant and is coupled to the activation only of cAMP but not of intracellular Ca2+. These data indicate that human colon tumor cells express PAC1 and are differentially coupled to intracellular signal transduction molecules. The ability to activate both cAMP and Ca2+ appears to be a prerequisite for activation of tumor proliferation, indicating a potentially important factor in how PACAP potentiates the growth of certain tumors.