title: In vivo expression patterns of survivin and its splicing variants in chronic liver disease and hepatocellular carcinoma.
abstract: OBJECTIVE
  Our aim was to clarify the significance of expression levels and post-transcriptional splicing patterns of survivin during multistep hepatocarcinogenesis and tumor progression.
  
  
  METHODS
  Using immunohistochemistry, we first elucidated the expression of survivin protein in tissues of hepatocellular carcinoma (HCC) and the adjacent non-cancerous tissues. Furthermore, we investigated survivin gene expression patterns in these tissues.
  
  
  RESULTS
  Survivin protein was expressed not only in most HCC tissues but also in some cirrhotic nodules. In non-cancerous regions, the levels of survivin mRNA increased in proportion to their stage of progression. Survivin protein was expressed mainly in periportal areas, where proliferating cells were localized. In HCC, mRNA levels of survivin and survivin Delta Ex3 correlated with high proliferative activity, whereas the levels of surviving 2B did not.
  
  
  CONCLUSIONS
  These findings of mRNA and protein expressions of survivin in chronically injured avers indicate that it has an important role in hepatocarcinogenesis. A lack of correlation between proliferative activity and survivin 2B mRNA levels in HCC is suggestive of a previous hypothesis that this variant decreases sruvivin function in a dominant negative manner. Thus, our data suggest different functions of these splicing variants and their important roles in tumor progression.
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto 602-8566, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Takashima
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nakajima
authors.forename: Michihisa
authors.initials: M
authors.lastname: Moriguchi
authors.forename: Satoru
authors.initials: S
authors.lastname: Sekoguchi
authors.forename: Taichiroh
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Katagishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.forename: Masahito
authors.initials: M
authors.lastname: Minami
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
authors.forename: Keizo
authors.initials: K
authors.lastname: Kagawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okanoue
mesh_terms: D017398:Alternative Splicing; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin