title: Six1 promotes proliferation of pancreatic cancer cells via upregulation of cyclin D1 expression.
abstract: Six1 is one of the transcription factors that act as master regulators of development and are frequently dysregulated in cancers. However, the role of Six1 in pancreatic cancer is not clear. Here we show that the relative expression of Six1 mRNA is increased in pancreatic cancer and correlated with advanced tumor stage. In vitro functional assays demonstrate that forced overexpression of Six1 significantly enhances the growth rate and proliferation ability of pancreatic cancer cells. Knockdown of endogenous Six1 decreases the proliferation of these cells dramatically. Furthermore, Six1 promotes the growth of pancreatic cancer cells in a xenograft assay. We also show that the gene encoding cyclin D1 is a direct transcriptional target of Six1 in pancreatic cancer cells. Overexpression of Six1 upregulates cyclin D1 mRNA and protein, and significantly enhances the activity of the cyclin D1 promoter in PANC-1 cells. We demonstrate that Six1 promotes cell cycle progression and proliferation by upregulation of cyclin D1. These data suggest that Six1 is overexpressed in pancreatic cancer and may contribute to the increased cell proliferation through upregulation of cyclin D1.
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Li
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.forename: Feng
authors.initials: F
authors.lastname: Lv
authors.forename: Yu
authors.initials: Y
authors.lastname: Chang
authors.forename: Xinhua
authors.initials: X
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Wang
authors.initials: W
authors.lastname: Ma
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wu
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D047369:Chromatin Immunoprecipitation; D019938:Cyclin D1 / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018398:Homeodomain Proteins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014410:Tumor Stem Cell Assay
chemical_list: D017931:DNA Primers; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C099236:SIX1 protein, human; D013778:Tetrazolium Salts; D013844:Thiazoles; D019938:Cyclin D1; C022616:thiazolyl blue; D001973:Bromodeoxyuridine