Cellular apoptosis susceptibility protein and proliferation in human hepatocellular carcinoma

Abstract

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 sudied 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.

Cross‐species hybridization of woodchuck hepatitis viral infection‐induced woodchuck hepatocellular carcinoma using human, rat and mouse oligonucleotide microarrays

“…Among the selected genes, PPIA 9 (peptidyl‐prolyl cis‐trans isomerase A), CDK4 26 and CSE1L 27 were shown to be upregulated in human HCC. CSE1L and CDK4 may play an important role in the development of HCC 28,29 . In contrast, RPL19 and GATA3 were overexpressed in human breast cancer 30 and pancreatic cancer, 31 respectively.…”

“…CSE1L and CDK4 may play an important role in the development of HCC. 28,29 In contrast, RPL19 and GATA3 were overexpressed in human breast cancer 30 and pancreatic cancer, 31 respectively. CDK4, RPL19, GATA3, CSE1L and APEX were shown to be prognostic markers.…”

Cellular apoptosis susceptibility (CSE1L/CAS) protein in cancer metastasis and chemotherapeutic drug-induced apoptosis

“…Another study showed that the immunohistochemical staining intensity score of CSE1L was significantly higher in human hepatocellular carcinoma than in non-tumor tissue ( p < 0.05) [43]. In breast cancer, benign lesions of the breast showed weak CSE1L staining, while 70% - 90% of breast tumor cells were heavily stained for CSE1L [9].…”

CSE1L (CSE1 chromosome segregation 1-like (yeast))

“…Study also showed that the immunohistochemical staining intensity score of CSE1L was significantly higher in human hepatocellular carcinoma than in non-tumor tissue (p < 0.05) Shiraki et al, 2006).…”