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  • Title: Expression of p53 protein and the apoptotic regulatory molecules Bcl-2, Bcl-XL, and Bax in locally advanced squamous cell carcinoma of the lung.
    Author: Shabnam MS, Srinivasan R, Wali A, Majumdar S, Joshi K, Behera D.
    Journal: Lung Cancer; 2004 Aug; 45(2):181-8. PubMed ID: 15246189.
    Abstract:
    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.
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