Premium
Overexpression of Calreticulin Contributes to the Development and Progression of Pancreatic Cancer
Author(s) -
Sheng Weiwei,
Chen Chuanping,
Dong Ming,
Zhou Jianping,
Liu Qingfeng,
Dong Qi,
Li Feng
Publication year - 2014
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24519
Subject(s) - calreticulin , cancer research , gene knockdown , mapk/erk pathway , pancreatic cancer , apoptosis , cell growth , biology , transfection , signal transduction , cancer , medicine , microbiology and biotechnology , cell culture , biochemistry , genetics , endoplasmic reticulum
We studied the clinicopathological significance for Calreticulin (CRT) expression in pancreatic cancer (PC), and its functional relationship with other signaling genes (especially with p53) in regulating the biological behavior of PC cells. IHC, IF, IB, and real‐time PCR were used to detect CRT expression in PC, while transfection and drug intervention were used to investigate the functional relationship of CRT with other signaling genes. IHC showed both CRT and p53 expression was significantly increased in PC, compared to that in paired non‐cancerous pancreatic tissues ( P < 0.001). High expression of CRT was positively associated with tumor UICC stage and lymph nodes metastasis ( P = 0.034 and P = 0.015), and was an independent adverse prognostic indicator in patients with PC. No relationship was found between CRT and p53 expression in spearman's rank correlation test. Altered expression of CRT did not change p53, MDM2, pho‐AKT, pho‐p38, and pho‐JNK expression, but had a specific regulation on pho‐ERK. Meanwhile, CRT‐regulated cell proliferation, migration, and invasion of PC cells in MEK/ERK pathway dependent manner. In addition, CRT knockdown significantly decreased pho‐ERK expression and cell chemoresistance independent of activated p53 and caspase‐3‐related apoptosis in gemcitabine‐ or oxaliplatin‐treated Capan‐2 cells. Our study first demonstrated that overexpression of CRT contributed to the development and progression of PC through MEK/ERK‐signaling pathway but independent of p53. The interaction between CRT and MEK/ERK pathway might provide a new idea for revealing malignant biology and supplying new gene targeted chemotherapy of PC. J. Cell. Physiol. 229: 887–897, 2014. © 2013 Wiley Periodicals, Inc.