Kayed H, Kleeff J, Ding J, Hammer J, Giese T, Zentgraf H, Büchler M W, Friess H
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Histol Histopathol. 2004 Oct;19(4):1021-31. doi: 10.14670/HH-19.1021.
Meningioma-associated protein, MAC30, is a protein with unknown function and cellular localization that is differentially expressed in certain malignancies. In the present study, the expression of MAC30 in a variety of normal and cancerous human gastrointestinal tissues, with special emphasis on pancreatic tissues was analyzed. Quantitative RT-PCR was utilized to compare MAC30 expression levels. In situ hybridization and immunohistochemistry were carried out to localize MAC30 mRNA and protein expression in normal and cancerous tissue samples of the esophagus, stomach, colon and pancreas. Furthermore, the effects of TGF-beta on the transcription of MAC30 mRNA were examined in pancreatic cancer cells. MAC30 mRNA was expressed in a wide variety of normal human tissues, being most abundant in testicular and gastric tissue samples. MAC30 mRNA levels were significantly increased in breast and colon cancer, but significantly decreased in pancreatic and renal cancer. TGF-beta down-regulated MAC30 mRNA levels in certain pancreatic cancer cells. MAC30 protein was localized in normal pancreatic tissues, mainly in acinar and islet cells, and in normal colon, gastric and esophageal tissues especially in the mucosal cells. MAC30 was strongly present in tubular complexes in pancreatic cancer tissues but weak to absent in pancreatic cancer cells of primary tumors and metastases. In contrast, esophageal, gastric and colon tumors displayed strong MAC30 immunoreactivity in the cancer cells. In conclusion, MAC30 is expressed in various normal and diseased human tissues. MAC30 up-regulation in certain tumors and down-regulation in others suggests that this protein plays a distinct role in human malignancies.
脑膜瘤相关蛋白MAC30是一种功能和细胞定位未知的蛋白质,在某些恶性肿瘤中差异表达。在本研究中,分析了MAC30在多种正常和癌性人类胃肠道组织中的表达情况,特别着重于胰腺组织。采用定量逆转录聚合酶链反应(qRT-PCR)比较MAC30的表达水平。进行原位杂交和免疫组织化学以定位MAC30 mRNA和蛋白质在食管、胃、结肠和胰腺的正常及癌组织样本中的表达。此外,在胰腺癌细胞中检测了转化生长因子-β(TGF-β)对MAC30 mRNA转录的影响。MAC30 mRNA在多种正常人类组织中表达,在睾丸和胃组织样本中最为丰富。MAC30 mRNA水平在乳腺癌和结肠癌中显著升高,但在胰腺癌和肾癌中显著降低。TGF-β在某些胰腺癌细胞中下调MAC30 mRNA水平。MAC30蛋白定位于正常胰腺组织,主要在腺泡和胰岛细胞中,在正常结肠、胃和食管组织中,尤其在黏膜细胞中。MAC30在胰腺癌组织的管状复合物中强烈表达,但在原发性肿瘤和转移灶的胰腺癌细胞中表达较弱或缺失。相反,食管、胃和结肠肿瘤在癌细胞中显示出强烈的MAC30免疫反应性。总之,MAC30在各种正常和患病的人类组织中表达。MAC30在某些肿瘤中的上调和在其他肿瘤中的下调表明该蛋白在人类恶性肿瘤中发挥着独特作用。