High hRFI expression correlates with resistance to fluoropyrimidines in human colon cancer cell lines and in xenografts.
We previously reported that the over-expression of hRFI, a protein preferentially expressed in the digestive tract regions of several cancers, exhibited a tendency to inhibit TNF-alpha induced apoptosis. In this study, we sought to determine the potential effect of hRFI expression on the sensitivity to 5-fluorouracil (5-FU) and/or other fluoropyrimidines. For the whole lysates of 8 colon cancer cell lines, we performed Western blotting with anti-hRFI antibody and analyzed the correlations between the expression level of hRFI and the cell lines' sensitivity to 5-FU induced apoptosis. Furthermore, for a tissue microarray consisting of 32 xenograft derived human cancer cell lines, we examined the expression levels of hRFI and survivin by immunohistochemical staining, and analyzed the correlations between the expression of each protein and the sensitivity to several chemotherapeutic agents in the xenografts examined. Both in colon cancer cell lines and in xenografts, the expression level of hRFI was correlated with resistance to 5-FU and its derivatives. This evidence suggests that hRFI may be a marker predicting the response to fluorouracil derived chemotherapeutic agents and that the reduction of the expression level of hRFI might improve the outcome of chemotherapy.
Sasaki
S
S
Dept. of Surgical Oncology, The University of Tokyo, Tokyo, Japan. SASAKI-1SU@h.u-tokyo.ac.jp
Watanabe
T
T
Kobunai
T
T
Konishi
T
T
Kitayama
J
J
Nagawa
H
H
D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D000077022:Survivin; D046888:Tissue Array Analysis; D014183:Transplantation, Heterologous
C107489:BIRC5 protein, human; D002352:Carrier Proteins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011743:Pyrimidines; C461219:RNF34 protein, human; D000077022:Survivin