Tanaka Ryota, Ishiyama Tadashi, Uchihara Teruhito, Inadome Yukinori, Iijima Tatsuo, Morishita Yukio, Kano Junko, Goya Tomoyuki, Noguchi Masayuki
Department of Thoracic Surgery, Gunma Prefectural Cancer Center, Gunma, and Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan.
Cancer. 2006 Feb 1;106(3):648-53. doi: 10.1002/cncr.21639.
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.
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.
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.
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.
程序性细胞死亡即凋亡的调控对于正常发育和体内稳态的维持至关重要。已有研究表明，新型抗凋亡蛋白Bax抑制剂-1（BI-1）代表了一种受Bcl-2和Bax控制的细胞死亡途径的新型调节因子。
从32例周围型腺癌患者中获取手术切除的肺标本，检测BI-1基因表达，并与p53、bcl-2和Bax基因的表达进行比较。
32个肿瘤中有14个（43.8%）通过原位杂交检测BI-1基因表达呈阳性。在伴有细支气管肺泡癌（BAC）的腺癌以及具有细支气管肺泡播散的混合亚型腺癌中，肿瘤标本中的BI-1基因表达（17个肿瘤中有14个；82.4%）明显高于无细支气管肺泡播散的癌。与BI-1阴性腺癌患者相比，BI-1阳性腺癌患者的预后相对较好。32个肿瘤中有11个（34.4%）p53蛋白呈阳性，32个肿瘤中只有1个（3.1%）Bcl-2蛋白呈阳性，32个肿瘤中有26个（81.3%）Bax蛋白呈阳性。通过免疫组织化学检测到的p53、Bcl-2和Bax的蛋白表达与BI-1基因表达无关。
BI-1基因表达局限于鳞屑样生长的肿瘤细胞，是周围型腺癌的一个预后因素。据信，BI-1基因表达在进化上是保守的，可能在BAC的凋亡途径中起关键调节作用。
