Cyclosporine A inhibits colorectal cancer proliferation probably by regulating expression levels of c-Myc, p21(WAF1/CIP1) and proliferating cell nuclear antigen.
The present study investigated the role of calcineurin (CaN) in the proliferation of human colorectal cancers. CaN activity and protein expression were increased in human colorectal cancers. Nuclear transcription factor NFAT, a physiological substrate for CaN, was activated in human colon cancer specimen as well as in the human colon cancer cell lines. CaN inhibitor cyclosporine A (CsA) reduced cell growth in these cell lines. CsA decreased the expressions of c-Myc and the proliferating cell nuclear antigen (PCNA) but also increased p21(WAF1/CIP1) expression. Our results suggest that CaN promotes colorectal cancer proliferation probably by regulating levels of c-Myc, p21(WAF1/CIP1), and PCNA.
Masuo
Takashige
T
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Japan.
Okamura
Shinichi
S
Zhang
Yajing
Y
Mori
Masatomo
M
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D050778:NFATC Transcription Factors / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D065095:Calcineurin Inhibitors; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; C489427:MYC protein, human; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D016572:Cyclosporine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019703:Calcineurin