Dephosphorylation of cancer protein by tyrosine phosphatases in response to analogs of luteinizing hormone-releasing hormone and somatostatin.
Protein phosphorylation/dephosphorylation of tyrosine residues is an important regulatory mechanism in cell growth and differentiation. Previously it has been reported that RC-160, an octapeptide analog of somatostatin, and [D-Trp6]LHRH, an agonist of luteinizing hormone-releasing hormone (LHRH), stimulate receptor-mediated activity of tyrosine phosphatases (PTP) and reverse growth promotion of the tyrosine kinase (PTK) class of oncogenes in tumor cells. The effect of RC-160 and [D-Trp6]LHRH on protein phosphorylation was further examined in surgical specimens of human carcinomas. Protein extracts of human ovarian, liver, breast and prostate tumor samples were preincubated with epidermal growth factor (EGF) (10(-7) M) with or without [D-Trp6]LHRH or RC-160 (10(-6) M) at 25 degrees C for 2 h, followed by incubation for 10 min with [gamma-32p]ATP. SDS-PAGE, Western blotting, autoradiography and densitometry were then used to quantify the phosphorylation level of individual protein bands. It was found that EGF enhanced, and [D-Trp6]LHRH and RC-160 reduced phosphorylation of a prominent 300-kDa band. Two proteins (65 and 60 kDa), involved in growth control in tumor cell lines, were also identified in this study. The homology of substrate phosphorylation between induced PTK and PTP in the presence of hormones provided evidence that these substrates might be identical or related in tumors. These findings, along with the previous cell culture results, suggest that many solid tumors may respond to treatment with analogues of somatostatin and LHRH. Collectively, the results further support the hypothesis that these 60-, 65- and 300-kDa protein substrates may be involved in growth-message transduction.
Lee
Lung-Ta
LT
Department of Nutrition and Health, ToKo University, Taiwan, P.R. China.
Schally
Andrew V
AV
Liebow
Charles
C
Lee
Ping-Ping
PP
Lee
Po-Huang
PH
Lee
Ming-Ting
MT
D000970:Antineoplastic Agents / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017329:Triptorelin Pamoate / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D009363:Neoplasm Proteins; D017329:Triptorelin Pamoate; C051458:vapreotide; D013004:Somatostatin; D004815:Epidermal Growth Factor; D017027:Protein Tyrosine Phosphatases