Effects of epidermal growth factor and analogues of luteinizing hormone-releasing hormone and somatostatin on phosphorylation and dephosphorylation of tyrosine residues of specific protein substrates in various tumors.
Effects of epidermal growth factor and analogues of luteinizing hormone-releasing hormone and somatostatin on phosphorylation and dephosphorylation of tyrosine residues of specific protein substrates in various tumors.
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DOI：
10.1073/pnas.88.5.1656
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发表时间：
1991-03
影响因子：
11.1
通讯作者：
Ming‐ting Lee;C. Liebow;A. Kamer;Schally Andrew
中科院分区：
文献类型：
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作者：
Ming‐ting Lee;C. Liebow;A. Kamer;Schally Andrew
生长抑素（SS）和促黄体生成素释放激素（LH-RH）的类似物激活MIA PaCa-2人胰腺癌细胞系膜上的酪氨酸磷酸酶并抑制生长。我们比较了在MIA PaCa-2（人胰腺癌）、HCPC（鼠颊袋癌）、A-549（人肺癌）、HT-29（人结肠癌）和R3230AC（乳腺癌）等癌细胞系中被表皮生长因子（EGF）磷酸化的底物和被SS类似物RC-160 （d - ph - cys - tyr - d - trp - lys - valys - cys - trp - nh2）和[D-Trp6] rh去磷酸化的底物。EGF磷酸化170、65和60 kDa的蛋白以及SS和LH-RH的类似物促进MIA PaCa-2和HCPC细胞系中这些蛋白的去磷酸化。EGF受体为170 kDa。已知pp60src （60 kDa）是EGF受体的底物。LH-RH受体也是60 kDa。RC-160和[D-Trp6] rh - rh的作用在数量上存在差异。对HT-29、A-549和R3230AC癌细胞系的检测显示，EGF没有磷酸化，RC-160和[D-Trp6]LH-RH也没有去磷酸化。除了170-、65-和60-kDa蛋白外，35-kDa蛋白在一些癌细胞中也被磷酸化。这项工作表明，SS和LH-RH的类似物可以在生物化学和功能上逆转EGF的作用。
Analogues of somatostatin (SS) and luteinizing hormone-releasing hormone (LH-RH) activate tyrosine phosphatases in MIA PaCa-2 human pancreatic cancer cell line membranes and inhibit growth. We compared the substrates phosphorylated by epidermal growth factor (EGF) to those dephosphorylated by the SS analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) and [D-Trp6]LH-RH in cancer cell lines such as MIA PaCa-2 (human pancreatic cancer), HCPC (hamster cheek pouch carcinoma), A-549 (human lung cancer), HT-29 (human colon cancer), and R3230AC (breast cancer). EGF phosphorylated proteins of 170, 65, and 60 kDa and analogues of SS and LH-RH promoted the dephosphorylation of these proteins in MIA PaCa-2 and HCPC cell lines. The EGF receptor is 170 kDa. pp60src (60 kDa) is known to be a substrate for EGF receptor. The LH-RH receptor is also 60 kDa. The effects of RC-160 and [D-Trp6]LH-RH were quantitatively different. Examinations of HT-29, A-549, and R3230AC cancer cell lines revealed no phosphorylation by EGF or dephosphorylation by RC-160 and [D-Trp6]LH-RH. In addition to the 170-, 65-, and 60-kDa proteins, 35-kDa proteins were also phosphorylated in some cancer cell lines. This work demonstrates that analogues of SS and LH-RH can reverse the effects of EGF biochemically as well as functionally.