Expression of Bcl-2 in lung neuroendocrine tumours: comparison with p53.
Several genetic aberrations have been implicated in the carcinogenesis of small cell lung carcinomas (SCLCs), including tumour suppressor gene p53 deletion and mutation and amplification of the myc family proto-oncogenes. However, their exact ontogeny and carcinogenesis remain unknown. There are no proven aetiological factors for lung carcinoid tumours. Recent evidence suggests that the genetic regulation of apoptosis is of critical importance during tumourigenesis and that oncogene and tumour suppressor genes can regulate the rate, or susceptibility, of cells to undergo apoptosis. In this study, the expression of Bcl-2 protein has been investigated in 77 primary lung neuroendocrine tumours, including 55 SCLCs and 22 carcinoid tumours, and compared with p53 expression. Of the 77 tumours studied, Bcl-2 immunoreactivity was present in 80 per cent of SCLCs, 43 per cent of typical, and 67 per cent of atypical carcinoid tumours with more than 10 per cent tumour cell positivity. Western and Northern blot analysis revealed that carcinoid tumours expressed the 26 kD protein and bcl-2 transcripts. Whereas 42 per cent of the SCLCs studied displayed p53 protein immunoreactivity in more than 10 per cent of tumour cells, p53 positivity was not found in lung carcinoid tumours. There are statistical differences in Bcl-2 and p53 expression between SCLCs and lung carcinoid tumours. These results suggest that disregulation of the genetic mechanisms controlling apoptosis is a critical step in the progression of SCLC, and the expression of Bcl-2 is involved in the pathogenesis of SCLC and lung carcinoid tumours. The genetic complementation of simultaneously deregulated Bcl-2 and p53 may be implicated in the multistep tumourigenesis of small cell lung cancer.
Wang
D G
DG
Division of Medicine, School of Clinical Medicine, Queen's University of Belfast, U.K.
Johnston
C F
CF
Sloan
J M
JM
Buchanan
K D
KD
D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D015153:Blotting, Western; D002276:Carcinoid Tumor / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D018358:Neuroendocrine Tumors / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53