Expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins in human retinoblastoma

Clin Exp Ophthalmol. 2015 Apr;43(3):259-67. doi: 10.1111/ceo.12397. Epub 2014 Aug 28.

Abstract

Background: Regulation of apoptosis is a complex process that involves a number of genes, including Bcl-2, Bcl-x, Bax and other Bcl-2 family members. The aim of the present study is to assess the expression of Bcl- 2 and Bax in retinoblastoma, and correlate them with clinical and histopathological parameters.

Methods: The expression of Bcl-2 and Bax proteins were examined using immunohistochemistry, Western blotting and reverse transcriptase-polymerase chain reaction in a series of 60 prospective cases of primary retinoblastoma tissues.

Results: Immunohistochemistry showed expression of Bcl-2 in 40/60 (66.6%), whereas Bax expression was found only in 18/60 (30%) cases, and these correlated with mRNA expression. The Western blotting results also correlated well with the immunohistochemical expression of Bcl-2 (25 kDa) and Bax (21 kDa) proteins. Bcl-2 was expressed in 96% (24/25) of invasive tumours and in 45.7% (16/35) of non-invasive tumours. Expression of Bcl-2 significantly correlated with tumour invasiveness (P = 0.0274) and poor differentiation (P = 0.0163), whereas loss of Bax correlated with massive choroidal invasion and Pathological Tumor-Node-Metastasis (pTNM) (P = 0.0341). However, no correlation was found between Bax and Bcl-2 expression.

Conclusions: Our findings suggest that these apoptotic regulatory proteins may serve as poor prognostic markers and can be used as a therapeutic target for the treatment of invasive retinoblastoma. Further functional studies are required to explore the role of Bax and Bcl-2 in retinoblastoma.

Keywords: Bax; Bcl-2; apoptosis; immunohistochemistry; retinoblastoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Child, Preschool
  • Female
  • Gene Expression / physiology
  • Genes, Neoplasm / physiology
  • Humans
  • Immunohistochemistry
  • Male
  • Neoplasm Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / genetics
  • Retinal Neoplasms / genetics
  • Retinal Neoplasms / metabolism*
  • Retinal Neoplasms / pathology
  • Retinoblastoma / genetics
  • Retinoblastoma / metabolism*
  • Retinoblastoma / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism*

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-2-Associated X Protein