Dephosphorylation of cancer protein by tyrosine phosphatases in response to analogs of luteinizing hormone-releasing hormone and somatostatin

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Published on Thursday, 19 September 2013

Abstract

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.

 

 

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See also:

- Somatostatin in oncology, the overlooked evidences;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature.