Cell motility and spreading promoted by CEACAM6 through cyclin D1/CDK4 in human pancreatic carcinoma.
Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) belongs to the human carcino-embryonic antigen (CEA) family. Numerous lines of studies have indicated that altered expression of CEACAM6 may have a role in carcinogenesis and development. However, few studies have defined functional roles and mechanisms of action. In the present study, the relationship between clinical and pathological parameters was also analyzed. The relative CEACAM6 protein expression of pancreatic carcinoma was significantly higher than that in non-cancerous tissue. Different clinical stages and lymph node metastasis between groups were significantly different (P<0.05). We used siRNA and forced-expression in multiple cell lines to define the role of CEACAM6 in the regulation of proliferation of pancreatic carcinoma in vitro and in vivo. Knockdown of endogenous CEACAM6 decreased proliferation of BxPC-3 and SW1990 cells. These changes significantly reduced cyclin D1 and CDK4 protein levels. Conversely, overexpression of CEACAM6 in MIA PaCa-2 cells stimulated proliferation and increased cyclin D1 and CDK4 protein levels. Our results confirm that CEACAM6 promoted cell proliferation, and these changes were mediated by cyclin D1/CDK4. These observations contribute to our understanding of the important roles of CEACAM6 in pancreatic carcinoma development and progression and could be a promising molecular target for the development of new diagnostic and therapeutic strategies of pancreatic carcinoma.
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Lu
L
Yan
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Yuan
Y
Wang
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Zhi-Zhi
ZZ
Wang
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Yan-Ting
YT
Rong
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Lin-Lin
LL
Chen
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Qian
Q
Li
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Ting
T
Liu
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Yong-Heng
YH
Chen
Department of Pathology, The First Affiliated Hospital, Xi'an Medical University, Xi'an, Shanxi 710077, P.R. China.
Yan-Dong
YD
Li
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Zhao-Hong
ZH
Huang
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Jie
J
Peng
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D018450:Disease Progression; D058851:GPI-Linked Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D019938:Cyclin D1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4