title: Cellular apoptosis susceptibility protein and proliferation in human hepatocellular carcinoma.
abstract: The cellular apoptosis susceptibility protein (CAS) is the human homologue of the product of the essential yeast chromosome segregation gene, CSE1, and has important roles in tumor necrosis factor (TNF)-induced apoptosis and cell proliferation. In this study, we used immunoblotting and immunohistochemistry to look at CAS expression in human hepatocellular carcinoma (HCC) cells. We also studied the correlation between CAS expression and cell proliferation. To do this, we studied the expression of proliferating cell nuclear antigen (PCNA) by immunostaining and at apoptosis by in situ nick end-labeling (TUNEL), followed by calculation of the PCNA labeling index (PCNA LI) and TUNEL labeling index (TUNEL LI). CAS was constitutively expressed in human HCC cell lines and was primarily confined to the cytoplasm of the cells. PCNA LI and TUNEL LI were significantly higher in HCC than in non-tumor tissue (p<0.01); however, the ratio of TUNEL LI/PCNA LI in HCC was significantly lower than that of non-tumor tissue. Immunohistochemistry revealed that the staining intensity score of CAS in HCC was significantly higher than that of non-tumor tissue (p<0.05). These results indicate that there is an augmentation of pro-liferative activity and apoptosis in HCC tissue, as compared to non-tumor tissue. There was a significant positive correlation between CAS and PCNA LI (p<0.05). In addition, we observed an inverse relationship between CAS expression and TUNEL LI, although the correlation did not reach statistical significance. These results suggest that CAS is expressed at higher levels in human HCC tissue than in non-tumor tissue. CAS may be associated with cell proliferation rather than apoptosis, and further, CAS might play an important role in the development of human HCCs.
authors.affiliation: First Department of Internal Medicine, Mie University School of Medicine, Mie 514-8507, Japan. katsuyas@clin.medic.mie-u.ac.jp
authors.forename: Katsuya
authors.initials: K
authors.lastname: Shiraki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Fujikawa
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ito
authors.forename: Takenari
authors.initials: T
authors.lastname: Yamanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Suzuki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yoneda
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Koujiro
authors.initials: K
authors.lastname: Takase
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D029563:Cellular Apoptosis Susceptibility Protein / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis
chemical_list: D029563:Cellular Apoptosis Susceptibility Protein; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen