Significance of COX-2 expression in human esophageal squamous cell carcinoma
Authors: Jian Zhang
Fang Ding
Chuannong Zhou
Min Wu
Zhihua Liu
Lin Wang
Qimin Zhan
Huiying Zhi
Aiping Luo
Journal: Carcinogenesis (2006)
Discipline: CLINICAL MEDICINE
Keywords: Cyclooxygenase-2 (COX-2); esophageal squamous cell carcinoma (ESCC); tumorigenesis; dysplasia; carcinoma in situ (CIS)
Affiliations: National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People's Republic of China.

Abstract:  Cyclooxygenase-2 (COX-2) is well established to play an important role in the tumorigenesis of a variety of human cancers; however, the function of COX-2 in the development of esophageal squamous cell carcinoma (ESCC) remains less clear. Here, we determined, first, the pattern of COX-2 expression in normal esophageal mucosa, dysplasia, carcinoma in situ (CIS) and invasive SCC. Immunohistochemical analysis showed that, while COX-2 was weakly expressed, if at all, in normal squamous epithelium, strong COX-2 expression was detected as early as the stage of dysplasia and frequently in 20 of 26 (77%) CIS and 86 of 111 (77%) invasive SCC. Upregulation of COX-2 in ESCC was found to be significantly associated with tumor progression (R = 0.493, P &lt; 0.01). Further, treatment of human ESCC cell lines (KYSE450 and KYSE510) with NS-398, a COX-2 specific chemical inhibitor, suppressed the production of prostaglandin E2 (PGE2) and induced cell growth inhibition, cell cycle arrest at the G1-S checkpoint, and the expression of cyclin-dependent kinase inhibitors p21waf1/cip1 and p27kip1. Finally, knockdown expression of COX-2 in KYSE450 cells by a specific COX-2 siRNA dramatically inhibited PGE2 production, cell growth and, more importantly, colony formation and tumorigenesis in nude mice. Together, this study suggested that COX-2 may be involved in an early stage of squamous cell carcinogenesis of the esophagus and has a non-redundant role in the regulation of cellular proliferation and tumorigenesis of esophageal epithelial cells. 

Retracted: No

PubPeer comments:
 Undeclared gel slice sites in Fig.4B (red arrow). Could authors give an explanation? ![file] , 
 Dear Dr. Takifugu Stictonotus, Thank you for your concern. In this experiment, KYSE450 cells were transfected with pSilencer -COX-2 or pSilencer control. After puromycin selection, we acquired approx. 30 stable clones. The effect of RNAi on COX-2 mRNA expression were examined in these clones by semi-quantitative RTu2013PCR analysis. Two clones (among 30) expressing low COX-2 were selected and used for the following function experiments. These two selected clones and control were not adjacent in the original gel. To show the knock down efficiency of these clones, these lanes were pasted together. We should have added a dashed line or white spacing to indicate lane spicing. We apologize for the confusion that it caused. Since we run a housekeeping gene (Gapdh) as an internal control on each lane, we can get a ratio of the band of COX-2 and Gapdh for each lane and compare it to the ratio of our control group. The splicing did not affect the result. Zhihua Liu ,