Expression of the Bax inhibitor-1 gene in pulmonary adenocarcinoma.
BACKGROUND
The regulation of programmed cell death, or apoptosis, is crucial for normal development and for the maintenance of homeostasis. It has been shown that the novel antiapoptotic protein Bax inhibitor-1 (BI-1) represents a new type of regulator of cell death pathways controlled by Bcl-2 and Bax.


METHODS
Surgically resected lung specimens were obtained from 32 patients with peripheral adenocarcinomas, and BI-1 gene expression was examined and compared with expression of the p53, bcl-2 and Bax genes.


RESULTS
Fourteen of 32 tumors (43.8%) were positive for BI-1 gene expression by in situ hybridization. BI-1 gene expression in tumor specimens was significantly higher in adenocarcinomas with bronchioloalveolar carcinoma (BAC) and in adenocarcinomas of mixed subtypes with bronchioloalveolar spreading (14 of 17 tumors; 82.4%) than in carcinomas without it spreading. Patients who had BI-1-positive adenocarcinoma showed a relatively favorable prognosis compared with patients who had BI-1-negative adenocarcinoma. Eleven of 32 tumors (34.4%) were positive for the p53 protein, only 1 of 32 tumors (3.1%) was positive for the Bcl-2 protein, and 26 of 32 tumors (81.3%) were positive for the Bax protein. Protein expressions of p53, Bcl-2, and Bax, as detected by immunohistochemistry, were not associated with BI-1 gene expression.


CONCLUSIONS
BI-1 gene expression was restricted to tumor cells with lepidic growth and was a prognostic factor for peripheral-type adenocarcinoma. It is believed that BI-1 gene expression is conserved evolutionarily and may act as a key regulator of the apoptotic pathway in BAC.
Tanaka
Ryota
R
Department of Thoracic Surgery, Gunma Prefectural Cancer Center, Gunma, and Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
Ishiyama
Tadashi
T
Uchihara
Teruhito
T
Inadome
Yukinori
Y
Iijima
Tatsuo
T
Morishita
Yukio
Y
Kano
Junko
J
Goya
Tomoyuki
T
Noguchi
Masayuki
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011379:Prognosis; D011506:Proteins / Q000032:analysis* / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; D011506:Proteins; C484209:TMBIM6 protein, human