Exogenous expression of hRFI induces multidrug resistance through escape from apoptosis in colorectal cancer cells.
BACKGROUND
hRFI is a newly discovered gene encoding a Ring Finger domain highly homologous to that of the X-chromosome-linked inhibitor of apoptosis protein, which is among the most potent inhibitors of apoptosis. The hRFI protein is preferentially expressed in colorectal cancers, although its actual function is unknown. The aim of this study was to determine whether hRFI possesses an anti-apoptotic function in colorectal cancer cells against chemotherapeutic agents.


METHODS
HCT116 colorectal cancer cells were exogenously transfected with hRFI or LacZ as a control. After exposure to either cisplatin, irinotecan or 5-fluorouracil, apoptosis and caspase-3 activity were evaluated by flow cytometry analysis.


RESULTS
The hRFI transfectant exhibited significant resistance to apoptosis induced by each of the three agents, along with inactivation of caspase-3. Growth in the normal medium was not altered.


CONCLUSIONS
hRFI plays an important role in the resistance to chemotherapeutic agent-induced apoptosis in colorectal cancer cells.
Konishi
Tsuyoshi
T
Department of Surgical Oncology, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Sasaki
Shin
S
Watanabe
Toshiaki
T
Kitayama
Joji
J
Nagawa
Hirokazu
H
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D000077146:Irinotecan; D014162:Transfection
D002352:Carrier Proteins; C461219:RNF34 protein, human; D000077146:Irinotecan; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin