Guo Xiao-Zhong, Xu Jian-Hua, Liu Min-Pei, Kleeff Jörg, Ho Choon-Kiat, Ren Li-Nan, Li Hong-Yu, Köninger Jörg, Cui Zhong-Min, Wang Di, Wu Chun-Yan, Zhao Jia-Jun, Friess Helmut
Department of Gastroenterology, Shenyang Northern Hospital, Shenyang, China.
Oncol Rep. 2005 Jul;14(1):59-63.
Decreased expression of the tumor suppressor gene, KAI1, is associated with metastasis formation in pancreatic cancer. The aim of the present study was to investigate whether KAI1 influences pancreatic cancer cell growth and colony formation. A full-length KAI1 cDNA expression vector was stably transfected into Panc-1 and MiaPaCa-2 pancreatic cancer cell lines. Transfection was confirmed by Western blot analysis and immunohistochemistry. Tumor cell growth and cell cycle distribution were determined by MTT cell growth assays, colony formation assays, and flow cytometric analysis. KAI1-transfected, but not control-transfected pancreatic cancer cells displayed cytoplasmic KAI1 immunoreactivity. Cell proliferation decreased in the KAI1-transfected cells compared to parental and control cells together with a Go/G1-phase cell cycle arrest. Colony formation was reduced by 2.6- and 3.5-fold in the KAI1-transfected Panc-1 and MiaPaCa-2 pancreatic cancer cells, respectively, compared with parental cells. KAI1 blocks pancreatic cancer cell growth through cell cycle arrest and inhibits anchorage-independent cell growth. These findings support the premise that KAI1 functions as a tumor suppressor in this malignancy.
肿瘤抑制基因KAI1的表达降低与胰腺癌转移的形成有关。本研究的目的是探讨KAI1是否影响胰腺癌细胞的生长和集落形成。将全长KAI1 cDNA表达载体稳定转染至Panc-1和MiaPaCa-2胰腺癌细胞系。通过蛋白质免疫印迹分析和免疫组织化学确认转染情况。通过MTT细胞生长试验、集落形成试验和流式细胞术分析来确定肿瘤细胞的生长和细胞周期分布。KAI1转染的胰腺癌细胞显示出细胞质KAI1免疫反应性，而对照转染的细胞则未显示。与亲本细胞和对照细胞相比，KAI1转染细胞的细胞增殖减少，同时出现G0/G1期细胞周期阻滞。与亲本细胞相比，KAI1转染的Panc-1和MiaPaCa-2胰腺癌细胞的集落形成分别减少了2.6倍和3.5倍。KAI1通过细胞周期阻滞来阻断胰腺癌细胞的生长，并抑制非锚定依赖性细胞生长。这些发现支持了KAI1在这种恶性肿瘤中起肿瘤抑制作用的前提。
