OBJECTIVE: Bcl-2 family of proteins plays a critical role in the regulation of apoptosis. This pathway may be dysregulated leading to an altered ratio of pro- and anti-apoptotic molecules, hence rendering cells resistant to chemotherapy. The objective of this study was to understand the role of Bcl-2 family members in mediation of apoptosis in squamous cell carcinoma of the lung. RESULTS: Bronchoscopically obtained lung biopsies from 30 cases of histologically proven squamous cell carcinoma of the lung in stage III were assessed for the expression of Bcl-2, Bcl-XL, and Bax at the mRNA and protein levels by semi-quantitative reverse transcription (RT-PCR) and immunohistochemistry. The apoptotic index (AI) was determined by the TUNEL assay. The AI ranged from <0.1 to 6.0% with a median of 1.3%. Bcl-2/Bax transcript ratio ranged from 1.5 to 4.5 and Bcl-XL/Bax from 1.3 to 4.0 indicating increased levels of anti-apoptotic molecules at the transcript levels. There was no correlation of the mRNA levels to the apoptotic index. (Wilcoxon-signed rank test.) Immunohistochemistry for proteins revealed that majority of the tumors were Bax predominated. p53 protein immunohistochemical expression was present in 66% cases. The apoptotic index correlated with Bax expression (P < 0.05; Wilcoxon-signed rank test and chi-square test) but not with Bcl-2, Bcl-XL or p53 levels. There was a positive association of p53 with Bax expression. CONCLUSION: The results of this study indicate that in locally advanced squamous cell carcinoma of the lung, Bax protein is up regulated and determines the level of apoptosis.
OBJECTIVE:Bcl-2 family of proteins plays a critical role in the regulation of apoptosis. This pathway may be dysregulated leading to an altered ratio of pro- and anti-apoptotic molecules, hence rendering cells resistant to chemotherapy. The objective of this study was to understand the role of Bcl-2 family members in mediation of apoptosis in squamous cell carcinoma of the lung. RESULTS: Bronchoscopically obtained lung biopsies from 30 cases of histologically proven squamous cell carcinoma of the lung in stage III were assessed for the expression of Bcl-2, Bcl-XL, and Bax at the mRNA and protein levels by semi-quantitative reverse transcription (RT-PCR) and immunohistochemistry. The apoptotic index (AI) was determined by the TUNEL assay. The AI ranged from <0.1 to 6.0% with a median of 1.3%. Bcl-2/Bax transcript ratio ranged from 1.5 to 4.5 and Bcl-XL/Bax from 1.3 to 4.0 indicating increased levels of anti-apoptotic molecules at the transcript levels. There was no correlation of the mRNA levels to the apoptotic index. (Wilcoxon-signed rank test.) Immunohistochemistry for proteins revealed that majority of the tumors were Bax predominated. p53 protein immunohistochemical expression was present in 66% cases. The apoptotic index correlated with Bax expression (P < 0.05; Wilcoxon-signed rank test and chi-square test) but not with Bcl-2, Bcl-XL or p53 levels. There was a positive association of p53 with Bax expression. CONCLUSION: The results of this study indicate that in locally advanced squamous cell carcinoma of the lung, Bax protein is up regulated and determines the level of apoptosis.
Authors: Andrés F Cardona; Leonardo Rojas; Beatriz Wills; Oscar Arrieta; Hernán Carranza; Carlos Vargas; Jorge Otero; Luis Corrales-Rodriguez; Claudio Martín; Noemí Reguart; Pilar Archila; July Rodríguez; Mauricio Cuello; Carlos Ortíz; Sandra Franco; Christian Rolfo; Rafael Rosell Journal: Oncotarget Date: 2016-09-19
Authors: I Paul; A D Chacko; I Stasik; S Busacca; N Crawford; F McCoy; N McTavish; B Wilson; M Barr; K J O'Byrne; D B Longley; D A Fennell Journal: Cell Death Dis Date: 2012-12-20 Impact factor: 8.469