Expression of p53 protein and the apoptotic regulatory molecules Bcl-2, Bcl-XL, and Bax in locally advanced squamous cell carcinoma of the lung.
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.


CONCLUSIONS
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.
Shabnam
Mir Snober
MS
Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Srinivasan
Radhika
R
Wali
Anjlina
A
Majumdar
Siddhartha
S
Joshi
Kusum
K
Behera
Digambar
D
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D001999:Bronchoscopy; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007194:India; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein