The breakdown of apoptotic mechanism in the development and progression of colorectal carcinoma.
BACKGROUND
Fas (APO-1/CD95) is a cell surface receptor that mediates apoptosis when it reacts with Fas ligand (FasL) or Fas antibody. Alterations of Fas and FasL expression have been demonstrated in various carcinomas.


METHODS
We examined the alteration of Fas and FasL expression in seventy-eight specimens of colorectal adenoma and carcinoma by immunohistochemistry and real-time reverse-transcriptase polymerase chain reaction (RT-PCR).


RESULTS
Our study revealed that the expression of Fas was reduced in colorectal adenoma and completely lost in some 60% of colorectal carcinomas. Fas expression was significantly down-regulated in liver metastasis compared with corresponding primary colorectal carcinoma. The expression of Fas significantly related to p53 status, tumor location and apoptosis in colorectal carcinoma. Up-regulation of FasL was not detected in colorectal adenoma, carcinoma cells and liver metastatic cancer cells.


CONCLUSIONS
These results indicate that Fas may play an important role, not only in development but also progression, and that FasL is not always required for both development and progression in colorectal carcinomas.
Nara Medical University, 840 Shi Jo-cho, Kashihara-city, Nara 634-8522, Japan. ogawasan@nmu-gw.naramed-u.ac.jp
Sanehito
S
Ogawa
Mitsuo
M
Nagao
Hiromichi
H
Kanehiro
Michiyoshi
M
Hisanaga
Saiho
S
Ko
Naoya
N
Ikeda
Yosiyuki
Y
Nakajima
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D015536:Down-Regulation; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019394:Ki-67 Antigen; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor