Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110001 China.
Hum Pathol. 2010 May;41(5):724-36. doi: 10.1016/j.humpath.2009.10.017. Epub 2010 Jan 25.
Bag-1 is an antiapoptotic protein with its altered expression and localization in malignancies. To clarify the role of Bag-1 in gastric carcinogenesis, its expression was examined by immunohistochemistry and in situ hybridization on a tissue microarray containing gastric carcinomas, adjacent nonneoplastic mucosa (NNM), adenomas, intestinal metaplasia (IM), or gastritis. Gastric carcinoma tissue and cell lines were studied for Bag-1 expression by Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). The results demonstrated that Bag-1 proteins were differentially expressed in the nucleus or cytosol of MKN28, AGS, MKN45, KATO-III, or HGC-27 cell lines, despite similar levels of messenger RNA (mRNA) expression. The Bag-1 mRNA overexpression was detectable in 73.3% of 15 gastric carcinomas without significant difference in its encoding products' levels. The nuclear Bag-1 expression gradually decreased from gastritis, IM, adenoma to carcinoma (P < .05), and negatively correlated with lymphatic invasion or lymph node metastasis, cytoplasmic Bag-1 expression, negative parafibromin expression, and poor prognosis (P < .05). Cytoplasmic Bag-1 was weakly immunoreactive in carcinomas, compared with gastritis (P < .05), and positively associated with invasive depth and poor prognosis of the carcinoma (P < .05). The positive rate of Bag-1 mRNA expression was higher in adjacent IMs than carcinomas or adjacent NNM (P < .05). Bag-1 mRNA was expressed more in carcinomas from female patients than the male counterparts (P < .05). There was a positive correlation of Bag-1 mRNA expression with invasive depth and venous invasion (P < .05). Our study indicated that aberrant expression and subcellular distribution of Bag-1 might play an important role in the malignant transformation of gastric epithelial cells and should be considered as a biomarker for gastric carcinogenesis, subsequent progression, and prognosis.
Bag-1 是一种抗凋亡蛋白，其在恶性肿瘤中的表达和定位发生了改变。为了阐明 Bag-1 在胃癌发生中的作用，我们通过免疫组织化学和组织微阵列中的原位杂交技术，检测了胃癌、相邻非肿瘤黏膜（NNM）、腺瘤、肠上皮化生（IM）或胃炎中 Bag-1 的表达。我们通过 Western blot 和逆转录聚合酶链反应（RT-PCR）研究了胃癌组织和细胞系中 Bag-1 的表达。结果表明，尽管 Bag-1 的信使 RNA（mRNA）表达水平相似，但在 MKN28、AGS、MKN45、KATO-III 或 HGC-27 细胞系中，Bag-1 蛋白在细胞核或细胞质中存在差异表达。在 15 例无显著差异的胃癌中，可检测到 Bag-1 mRNA 过表达。核 Bag-1 表达从胃炎、IM、腺瘤逐渐减少至癌（P <.05），与淋巴浸润或淋巴结转移、细胞质 Bag-1 表达、阴性 parafibromin 表达和不良预后呈负相关（P <.05）。与胃炎相比，癌组织中细胞质 Bag-1 的免疫反应较弱（P <.05），与癌的浸润深度和不良预后呈正相关（P <.05）。Bag-1 mRNA 在癌旁 IM 中的表达阳性率高于癌或癌旁 NNM（P <.05）。女性患者癌中 Bag-1 mRNA 的表达高于男性患者（P <.05）。Bag-1 mRNA 的表达与浸润深度和静脉侵犯呈正相关（P <.05）。我们的研究表明，Bag-1 的异常表达和亚细胞分布可能在胃上皮细胞的恶性转化中发挥重要作用，应将其视为胃癌发生、后续进展和预后的生物标志物。
