title: RACK1 overexpression associates with pancreatic ductal adenocarcinoma growth and poor prognosis.
abstract: OBJECTIVE
  The receptor for activated protein kinase C (RACK1) is a scaffold protein involved in multiple intracellular signal pathways. Previous studies have shown that RACK1 is associated with the progression of multiple cancer types, including hepatocellular carcinoma and gastric cancer. However, the role of RACK1 in human pancreatic ductal adenocarcinoma (PDAC) remains unclear.
  
  
  METHODS
  In this study, the expression of RACK1 was evaluated by Western blot analysis in 8 paired fresh PDAC tissues and immunohistochemistry on 179 paraffin-embedded slices. Then, we used Fisher exact test to analyze the correlation between RACK1 expression and clinicopathological characteristics. Starvation and re-feeding assay was used to assess cell cycle. Western blot, CCK8, flow cytometry assays, and colony formation analyses demonstrated that RACK1 played an essential role in PDAC development. Annexin-V/PI apoptotic assay and western blot showed that RACK1 was involved in regulating the apoptosis of PDAC cells.
  
  
  RESULTS
  RACK1 was highly expressed in PDAC tissues and cell lines and was significantly associated with multiple clinicopathological factors. Univariate and multivariate analyses showed that high RACK1 expression was identified to be an independent prognostic factor for PDAC patients' survival. In vitro, serum starvation-refeeding experiment suggested that RACK1 was upregulated in proliferating PDAC cells, together with the percentage of cells at the S phase, and was correlated with the expression of Cyclin D1. Moreover, Overexpression of RACK1 facilitated the proliferation and cell cycle progression of PDAC cells, while downregulation of RACK1 induced growth impairment, G1/S cell cycle arrest and apoptosis in PDAC cells. Silencing RACK1 decreased bcl-2 expression, increased cleaved caspase3 expression level and induced the apoptosis of PDAC cells.
  
  
  CONCLUSIONS
  Our results suggest that RACK1 could play an important role in the tumorigenesis of PDAC and serve as a potential therapeutical target in PDAC treatment.
authors: Department of General Surgey, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors: Xiaohong
authors: X
authors: Li
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu, China.
authors: Ying
authors: Y
authors: Xiao
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors: Shaoqing
authors: S
authors: Fan
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors: Mingbing
authors: M
authors: Xiao
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors: Xiaotong
authors: X
authors: Wang
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors: Xudong
authors: X
authors: Chen
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors: Chunsun
authors: C
authors: Li
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226001, Jiangsu, China.
authors: Guijuan
authors: G
authors: Zong
authors: Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China. Electronic address: zhougx@ntu.edu.cn.
authors: Guoxiong
authors: G
authors: Zhou
authors: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu, China; Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226001, Jiangsu, China. Electronic address: Chwan@ntu.edu.cn.
authors: Chunhua
authors: C
authors: Wan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins
keywords: Cell proliferation; Pancreatic ductal adenocarcinoma (PDAC); Prognosis; RACK1