Differential roles of cyclin D1 and D3 in pancreatic ductal adenocarcinoma

Molecular Cancer

Research

Wing Xie¹  Dan Strumpf¹  Igor Jurisica²  Nhu-An Pham³  Nikolina Radulovich⁴  Ming-Sound Tsao⁵  Lisa Leung⁶ 

[1] Campbell Family Institute for Cancer Research, PMH, University Health Network, 101 College St., TMDT, M5G 1L7, Toronto, Ontario, Canada;Department of Medical Biophysics, Ontario Cancer Institute, Princess Margaret Hospital, 610 University Avenue, M5G 2M9, Toronto, Ontario, Canada;Department of Computer Science, University of Toronto, 6 King's College Rd., M5S 1A4, Toronto, Ontario, Canada;Ontario Cancer Institute and Princess Margaret Hospital, University Health Network, M5G 2M9, Toronto, Ontario, Canada;Ontario Cancer Institute and Princess Margaret Hospital, University Health Network, M5G 2M9, Toronto, Ontario, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, M5S 1A8, Toronto, Ontario, Canada;Ontario Cancer Institute and Princess Margaret Hospital, University Health Network, M5G 2M9, Toronto, Ontario, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, M5S 1A8, Toronto, Ontario, Canada;Department of Medical Biophysics, Ontario Cancer Institute, Princess Margaret Hospital, 610 University Avenue, M5G 2M9, Toronto, Ontario, Canada;Ontario Cancer Institute and Princess Margaret Hospital, University Health Network, M5G 2M9, Toronto, Ontario, Canada;Department of Medical Biophysics, Ontario Cancer Institute, Princess Margaret Hospital, 610 University Avenue, M5G 2M9, Toronto, Ontario, Canada;

关键词: Gene Ontology;    Pancreatic Ductal Adenocarcinoma;    KEGG Pathway;    PANC1 Cell;    Pancreatic Cancer Cell Line;   

DOI  :  10.1186/1476-4598-9-24

 received in 2009-06-22, accepted in 2010-02-01,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe cyclin D1 (CCND1) and cyclin D3 (CCND3) are frequently co-overexpressed in pancreatic ductal adenocarcinoma (PDAC). Here we examine their differential roles in PDAC.ResultsCCND1 and CCND3 expression were selectively suppressed by shRNA in PDAC cell lines with expression levels of equal CCND1 and CCND3 (BxPC3), enhanced CCND1 (HPAC) or enhanced CCND3 (PANC1). Suppression of cell proliferation was greater with CCND3 than CCND1 downregulation. CCND3 suppression led to a reduced level of phosphorylated retinoblastoma protein (Ser795p-Rb/p110) and resulted in decreased levels of cyclin A mRNA and protein. A global gene expression analysis identified deregulated genes in D1- or D3-cyclin siRNA-treated PANC1 cells. The downregulated gene targets in CCND3 suppressed cells were significantly enriched in cell cycle associated processes (p < 0.005). In contrast, focal adhesion/actin cytoskeleton, MAPK and NF B signaling appeared to characterize the target genes and their interacting proteins in CCND1 suppressed PANC1 cells.ConclusionsOur results suggest that CCND3 is the primary driver of the cell cycle, in cooperation with CCND1 that integrates extracellular mitogenic signaling. We also present evidence that CCND1 plays a role in tumor cell migration. The results provide novel insights for common and differential targets of CCND1 and CCND3 overexpression during pancreatic duct cell carcinogenesis.

【 授权许可】

Unknown   
© Radulovich et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.