Potential role of bcl-2 as a suppressor of tumour angiogenesis in non-small-cell lung cancer

Int J Cancer. 1997 Dec 19;74(6):565-70. doi: 10.1002/(sici)1097-0215(19971219)74:6<565::aid-ijc1>3.0.co;2-s.


It has been reported that genes regulating apoptosis may play a role in tumoral angiogenesis. This study examined the relationship between tumour vascularization, a measure of tumour angiogenesis, and bcl-2 and p53 expression in operable non-small-cell lung cancer (NSCLC). The relationship between bcl-2, p53 and tumour vascularization and epidermal-growth-factor-receptor(EGFR) and c-erbB-2 expression was also studied. Tissue sections from resected tumour specimens of 107 NSCLC patients were evaluated immunohistochemically for vascular grade and bcl-2, p53, EGFR and c-erbB-2 expression. bcl-2 expression was found in 20/107 (19%) cases and was associated with squamous-cell histology (p = 0.03). A strong inverse relationship was found between bcl-2 expression and vascular grade (p = 0.005). All c-erbB-2-positive cases were negative for bcl-2 expression (p = 0.01). Overall no association was found between c-erbB-2 expression and vascular grade. However, in bcl-2-negative cases positive c-erbB-2 expression correlated with low angiogenesis (p = 0.05). No relationship was found between p53 and EGFR expression and bcl-2, c-erbB-2 or vascular grade. The improved prognosis reported in bcl-2-positive NSCLC may be related to low tumour vascularization. The results suggest that the anti-apoptotic gene bcl-2 plays a role in regulating tumour angiogenesis. Since normal lung epithelium expresses bcl-2, a sequence of tumour progression involving loss of bcl-2, then activation of c-erbB-2 or increase in tumour vascularization is proposed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Carcinoma, Non-Small-Cell Lung / blood supply*
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / genetics
  • Female
  • Gene Expression
  • Genes, Tumor Suppressor / physiology*
  • Genes, bcl-2 / physiology*
  • Genes, p53 / physiology
  • Humans
  • Lung Neoplasms / blood supply*
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / genetics
  • Retrospective Studies
  • Survival Analysis
  • Tumor Suppressor Protein p53 / biosynthesis


  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases