bcl-2 and c-erbB-2 proteins are involved in the regulation of VEGF and of thymidine phosphorylase angiogenic activity in non-small-cell lung cancer

Koukourakis, M. I., Giatromanolaki, A., O'Byrne, Kenneth J., Jiles, C., Krammer, B., Gatter, K. C., & Harris, A. L. (1999) bcl-2 and c-erbB-2 proteins are involved in the regulation of VEGF and of thymidine phosphorylase angiogenic activity in non-small-cell lung cancer. Clinical and Experimental Metastasis, 17(7), pp. 545-554.

View at publisher

Abstract

Tumour angiogenesis has been recently recognised as one of the most important prognostic factors in lung cancer. Although a variety of angiogenic factors have been identified, the angiogenesis process remains poorly understood. Bcl-2, c-erbB-2 and p53 are well-known oncogenes involved in non- small-cell lung cancer pathogenesis. A direct correlation of thymidine phosphorylase (TP) and of vascular endothelial growth factor (VEGF) with intratumoural angiogenesis has been reported. In the present study we investigated the possible regulatory role if bcl-2, c-erB-2 proteins in angiogenesis and in VEGF and TP expression in non-small-cell lung cancer. Two hundred sixteen specimens from T1,2-NO, 1 staged patients treated with surgery alone were immunohistochemically examined. Bcl-2 and c-erbB-2 were significantly inversely related to each other (P = 0.04) and both were inversely associated with microvessel density (P < 0.02). High TP and VEGF reactivity was statistically related to loss of bcl-2 expression (P < 0.01). A significant co-expression of c-erbB-2 with TP was noted (P = 0.01). However, TP expression was related to high angiogenesis only in cases with absence of c-erB-2 expression (P < 0.0001). c-erbB-2 expression in poorly vascularised tumours was linked with poor outcome (P = 0.03). The present study provides strong evidence that the bcl-2 gene has a suppressive function over genes involved in both angiogenesis (VEGF and TP) and cell migration (c- erbB-2) in NSCLC. TP and c-erbB-2 proteins are significantly, and often simultaneously, expressed in bcl-2 negative cases. However, expression of the c-erbB-2 abolishes the TP-related angiogenic activity. Whether this is a result of a direct activity of the c-erbB-2 protein or a consequence of a c- erbB-2-related immune response remains to be further investigated.

Impact and interest:

43 citations in Scopus
Search Google Scholar™
39 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 65175
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Angiongenesis, bcl-2, c-erB-2, Non-small-cell lung cancer, epidermal growth factor receptor 2, oncoprotein, protein bcl 2, thymidine phosphorylase, unclassified drug, vasculotropin, angiogenesis, article, controlled study, enzyme activity, human, human tissue, lung non small cell cancer, prognosis, protein expression, regulatory mechanism, signal transduction, tumor vascularization, Aged, Carcinoma, Non-Small-Cell Lung, Endothelial Growth Factors, Female, Humans, Immunoenzyme Techniques, Life Tables, Lung Neoplasms, Lymphokines, Male, Middle Aged, Neoplasm Proteins, Neovascularization, Pathologic, Observer Variation, Proto-Oncogene Proteins c-bcl-2, Receptor, erbB-2, Retrospective Studies, Survival Analysis, Treatment Outcome, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors
DOI: 10.1023/A:1006780710148
ISSN: 0262-0898
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 1999 Springer Netherlands
Deposited On: 06 Dec 2013 02:09
Last Modified: 06 Dec 2013 02:09

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page