The expression of antiapoptotic proteins Bcl-2, Bcl-X(L), and Mcl-1 in benign, dysplastic, and malignant biliary epithelium.
OBJECTIVE
Cholangiocarcinoma can be cured by surgery, but only in a minority of cases. The activation of apoptosis is a major mode of action of chemotherapy and radiotherapy, which have limited benefit in the treatment of cholangiocarcinoma. The antiapoptotic members of the Bcl-2 protein family (Bcl-2, Bcl-X(L), and Mcl-1) are important inhibitors of apoptosis, but have not been investigated extensively in cholangiocarcinoma.


METHODS
The expression of Bcl-2, Bcl-X(L), and Mcl-1 was investigated in normal biliary epithelium (17), biliary dysplasia (three), and invasive cholangiocarcinoma (51), in addition to three human cholangiocarcinoma cell lines, by immunohistochemistry and immunofluorescence.


RESULTS
The expression of Bcl-2 was not detected in normal or malignant biliary tissue. In contrast, granular cytoplasmic Bcl-X(L) and Mcl-1 staining was found in 60-100% of cells in all normal, dysplastic, and malignant specimens, including the human cell lines examined in this study.


CONCLUSIONS
These findings indicate that Mcl-1 and Bcl-X(L), but not Bcl-2, are involved in the survival of normal and neoplastic cells in the biliary tree. By prolonging survival through blocking apoptosis, these proteins might be reducing the efficacy of cytotoxic anticancer treatments in cholangiocarcinoma.
Okaro
A C
AC
Department of Surgery, Royal Free Campus RF and UCMS, Pond Street, London NW3 2QG, UK.
Deery
A R
AR
Hutchins
R R
RR
Davidson
B R
BR
D017209:Apoptosis / Q000502:physiology*; D001650:Bile Duct Neoplasms / Q000737:chemistry*; D001652:Bile Ducts / Q000737:chemistry; D002460:Cell Line; D018281:Cholangiocarcinoma / Q000737:chemistry*; D004847:Epithelial Cells / Q000737:chemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000032:analysis*; D011230:Precancerous Conditions / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein