title: LRH1 as a driving factor in pancreatic cancer growth.
abstract: Liver receptor homolog 1 (LRH1), directs the development and differentiation of embryonic pancreas, and is overexpressed in pancreatic cancer (PC). We hypothesized that LRH1 promotes PC growth. Cell proliferation and tumorigenicity in nude mice were compared between empty vector-transfected (control) and stable LRH1-overexpressed PC cell lines. The subsequent tumor burden, vasculature development, and histologic features were evaluated. LRH1 overexpression enhanced the expression of downstream target genes (cyclin D1/E1) and stimulated cell proliferation in PC cell lines. LRH1 upregulated cyclin E1 truncated T1/T2 isoforms expression which may occur through ERα-calpain1 signaling. Compared with the control, LRH1 overexpressing stable cells generated tumors with increased weight, proliferation index and enhanced angiogenesis. Cyclin D1/E1 and calpain1 were overexpressed in human PC tumors compared to adjacent normal pancreas. These observations demonstrate that LRH1 promotes PC growth and angiogenesis, suggesting that LRH1 is a driving factor in tumorigenesis and may serve as a potential therapeutic target.
authors: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881, United States.
authors: Qiushi
authors: Q
authors: Lin
authors: Division of Gastroenterology and Liver Research Center, Rhode Island Hospital, Warren Alpert Medical School, Brown University, United States.
authors: Arihiro
authors: A
authors: Aihara
authors: Division of Gastroenterology and Liver Research Center, Rhode Island Hospital, Warren Alpert Medical School, Brown University, United States.
authors: Waihong
authors: W
authors: Chung
authors: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881, United States; Bacteriologic Laboratory, Harbin Center for Disease Control and Prevention, Harbin 150056, Heilongjiang Province, China.
authors: Yu
authors: Y
authors: Li
authors: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881, United States.
authors: Zheping
authors: Z
authors: Huang
authors: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881, United States; Department of Internal Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin 150040, Heilongjiang Province, China.
authors: Xuesong
authors: X
authors: Chen
authors: Department of Occupational Health Assessment, Shenzhen Prevention and Treatment Center for Occupational Diseases, Shenzhen 518001, Guangdong Province, China.
authors: Shaofan
authors: S
authors: Weng
authors: Division of Gastroenterology and Liver Research Center, Rhode Island Hospital, Warren Alpert Medical School, Brown University, United States.
authors: Rolf I
authors: RI
authors: Carlson
authors: Division of Gastroenterology and Liver Research Center, Rhode Island Hospital, Warren Alpert Medical School, Brown University, United States.
authors: Jack R
authors: JR
authors: Wands
authors: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881, United States. Electronic address: xiaoqun_dong@mail.uri.edu.
authors: Xiaoqun
authors: X
authors: Dong
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D056945:Hep G2 Cells; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C082631:NR5A2 protein, human; D018160:Receptors, Cytoplasmic and Nuclear
keywords: Cyclin D1; Cyclin E1; Liver receptor homolog 1; Pancreatic cancer