title: Association of gankyrin and stemness factor expression in human colorectal cancer.
abstract: BACKGROUND
  It is widely accepted that the adenoma-carcinoma sequence represents the process by which most colorectal cancers (CRCs) arise. Although gankyrin is overexpressed in CRC tissues, its roles in the initiation step of colorectal carcinogenesis remain largely unexplored.
  
  
  OBJECTIVE
  We investigated the expression of gankyrin and stemness factors in human colorectal adenomas, precancerous lesions, as well as CRC tissues to assess its involvement in colorectal carcinogenesis.
  
  
  METHODS
  Expression of several molecules including gankyrin and certain stemness factors was compared in 50 pairs of adenoma and surrounding normal mucosa using real-time quantitative polymerase chain reaction and in 30 CRC tissues using immunohistochemistry.
  
  
  RESULTS
  In CRC specimens, expression of CD133, a cancer stem cell marker, was significantly correlated with gankyrin expression. Gankyrin knockdown decreased the expression of vascular endothelial growth factor (VEGF) and stemness factors such as Nanog and Oct-4 in colorectal cancer cells. Expression of gankyrin and these stemness factors was significantly higher in adenomas than in the surrounding normal mucosa. Importantly, a significant correlation was observed between the expression of gankyrin, VEGF, and Nanog in colorectal adenomas.
  
  
  CONCLUSIONS
  In CRC development, gankyrin would control stem cell behavior by regulating the expression of stemness factors.
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Mine
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Sakurai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kashida
authors.forename: Shigenaga
authors.initials: S
authors.lastname: Matsui
authors.forename: Naoshi
authors.initials: N
authors.lastname: Nishida
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nagai
authors.forename: Satoru
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Watanabe
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
mesh_terms: D000071916:AC133 Antigen; D000236:Adenoma / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D013234:Stem Cells / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D009687:Nuclear Proteins; C000606023:PROM1 protein, human; C403591:PSMD10 protein, human; D010455:Peptides; D011518:Proto-Oncogene Proteins; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt; D046988:Proteasome Endopeptidase Complex