Expression of HSP70, Bcl-2, and Bcl-xL in Primary Colorectal Carcinoma Cell Lines and Tissues

초록

The 70-kD heat shock protein (HSP 70) is thought to be involved in protein-protein interaction, including oncogenic products. The Bcl-2 family proteins regulate a distal step in an evolutionary conserved pathway for programmed cell death. Among these, Bcl-2 and Bcl-xL are thought to prevent apoptosis, however, these two proteins appeared to have a different role in carcinogenesis and pregression. To elucidate a role of this protein in human colorectal carcinomas, we have investigated HSP70, Bcl-2, and Bcl-xL expression by Western blot analysis. HSP70 was expressed in all 4 colon cancer cell lines (clone A, MIP101, CX-1, HT-29) but more prominent in CX-1 and HT-29 which were known to have a high metastatic potential. In contrast, Bcl-2 and Bcl-xL were more strongly expressed in clone A and MIP101, which were known to have a low metastatic potential. Immunohistochemistry was performed in 73 normal colonic mucosal tissues, 5 tubular adenomas, and 73 colon carcinoma tissues. In the normal colonic mucosa, Bcl-2-positive epithelial cells tended to be located at the base of the crypts, while the HSP70 and Bcl-xL-positive epithelial cells tended to be located at the luminal surface. The intracellular expression patterns of Bcl-2 was diffuse cytoplasmic, whereas those of Bcl-xL was granular cytoplasmic. Fifty eight(79.45%), 30(41.10%), and 71(97.2%) of 73 cases showed HSP70, Bcl-2, and Bcl-xL expression. The percentage of Bcl-2 immunoreactive cells was generally lower in carcinomas than in adenomas, whereas Bcl-xL immunoreactive cells appeared to be higher in carcinoma. The expression of HSp70 tended to be higher in cases with positive lymph node metastasis (p=0.001) or advanced stage (p=0.002). In contrast, Bcl-2 expression tended to be higher in cases with advanced clinical stage (p=0.048). The expression of HSP70, Bcl-2, or Bcl-xL did not show any relationship with location, tumor size, differentiation, or depth of invasion. These results suggest that HSP70 expression may