Guo X, Friess H, Graber H U, Kashiwagi M, Zimmermann A, Korc M, Büchler M W
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
Cancer Res. 1996 Nov 1;56(21):4876-80.
KAI1 is a metastasis suppressor gene for prostate cancer that is located on chromosome 11p11.2-13. Using Northern blot analysis and in situ hybridization, we studied expression of KAI1 mRNA in specimens from 14 normal pancreases and 27 primary pancreatic cancers, and then correlated the findings with the clinical and histopathological parameters of the patients. Northern blot analysis showed increased steady-state levels of KAI1 mRNA expression in 24 of 27 (89%) pancreatic cancer samples. In situ hybridization showed enhanced KAI1 mRNA levels in the pancreatic cancer cells in 82% cancer tissues. The stroma surrounding the cancer mass and normal pancreatic tissue adjacent to the cancer cells exhibited very low levels of KAI1 mRNA expression. Correlation of the mRNA levels obtained by Northern blot analysis with clinical parameters of the patients revealed that KAI1 mRNA levels were significantly higher (P < 0.01) in earlier tumor stages (I, II), compared with advanced tumor stages (III, IV) in which lymph node or distant metastases were present. Furthermore, poorly differentiated tumors had significantly higher KAI1 mRNA levels than those that were moderately or well differentiated (P < 0.05). No association between KAI1 expression and survival was found. Our results indicate that KAI1 mRNA expression is reduced in patients with advanced tumor stages. This suggests that reduction of KAI1 expression might enable pancreatic cancer cells to spread in lymph nodes and to distant organs.
KAI1是一种位于11号染色体p11.2 - 13区域的前列腺癌转移抑制基因。我们运用Northern印迹分析和原位杂交技术，研究了14例正常胰腺组织标本和27例原发性胰腺癌组织标本中KAI1 mRNA的表达情况，并将研究结果与患者的临床及组织病理学参数进行关联分析。Northern印迹分析显示，27例胰腺癌样本中有24例（89%）KAI1 mRNA表达的稳态水平升高。原位杂交显示，82%的癌组织中胰腺癌细胞内KAI1 mRNA水平增强。癌块周围的间质以及癌细胞旁的正常胰腺组织中KAI1 mRNA表达水平极低。通过Northern印迹分析获得的mRNA水平与患者临床参数的关联分析显示，与存在淋巴结转移或远处转移的晚期肿瘤阶段（III、IV期）相比，早期肿瘤阶段（I、II期）的KAI1 mRNA水平显著更高（P < 0.01）。此外，低分化肿瘤的KAI1 mRNA水平显著高于中分化或高分化肿瘤（P < 0.05）。未发现KAI1表达与生存率之间存在关联。我们的结果表明，晚期肿瘤阶段患者的KAI1 mRNA表达降低。这表明KAI1表达的降低可能使胰腺癌细胞能够在淋巴结和远处器官扩散。
