Hsi L C, Baek S J, Eling T E
Eicosanoid Biochemistry Section, Laboratory of Molecular Carcinogenesis, Research Triangle Park, North Carolina 27709, USA.
Exp Cell Res. 2000 May 1;256(2):563-70. doi: 10.1006/excr.2000.4863.
Induction of cyclooxygenase-2 (COX-2) is an early event in the sequence of polyp formation to colon carcinogenesis. COX-2 is at elevated levels in human colorectal cancers and in tumors and polyps of mouse models of colorectal cancer. Mutation of the adenomatous polyposis coli (APC) gene is the initial event leading to colorectal cancer. Colorectal cells in culture which express mutant APC are often used to examine the association of COX-2 expression and apoptosis. The expression of full-length APC in HT-29 cells, a human colorectal carcinoma cell line which normally expresses truncated APC and highly expresses COX-2, inhibits cell growth through increased apoptosis and results in a down-regulation of COX-2 protein. In this report, we examine whether down-regulation of COX-2 is directly linked to the increase in apoptosis observed in these HT-29-APC cells. We present evidence that COX-2 and apoptosis are not linked since COX-2, although expressed, is catalytically inactive. Interestingly, the COX-2 cloned from HT-29 cells is catalytically active when transfected into HCT-116 cells, a colorectal cell line which normally does not express COX-2, but is not active in the HT-29 cell line itself.
环氧化酶-2（COX-2）的诱导是从息肉形成到结肠癌发生这一序列中的早期事件。COX-2在人类结直肠癌以及结直肠癌小鼠模型的肿瘤和息肉中水平升高。腺瘤性息肉病 coli（APC）基因的突变是导致结直肠癌的起始事件。培养中表达突变型APC的结肠直肠细胞常被用于研究COX-2表达与细胞凋亡的关联。在HT-29细胞（一种通常表达截短型APC且高表达COX-2的人类结肠癌细胞系）中全长APC的表达，通过增加细胞凋亡来抑制细胞生长，并导致COX-2蛋白的下调。在本报告中，我们研究COX-2的下调是否与在这些HT-29-APC细胞中观察到的细胞凋亡增加直接相关。我们提供的证据表明COX-2与细胞凋亡没有关联，因为COX-2尽管有表达，但催化无活性。有趣的是，从HT-29细胞克隆的COX-2转染到通常不表达COX-2的结肠直肠细胞系HCT-116细胞中时具有催化活性，但在HT-29细胞系自身中无活性。
