In vivo expression patterns of survivin and its splicing variants in chronic liver disease and hepatocellular carcinoma.
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.
Takashima
Hidetaka
H
Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto 602-8566, Japan.
Nakajima
Tomoki
T
Moriguchi
Michihisa
M
Sekoguchi
Satoru
S
Nishikawa
Taichiroh
T
Watanabe
Tadashi
T
Katagishi
Tatsuo
T
Kimura
Hiroyuki
H
Minami
Masahito
M
Itoh
Yoshito
Y
Kagawa
Keizo
K
Okanoue
Takeshi
T
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
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin