Wild-type APC regulates caveolin-1 expression in human colon adenocarcinoma cell lines via FOXO1a and C-myc.
Genetic evidence suggests that caveolin-1, an essential component of membrane caveolae, acts as a tumor promoter in some, and a tumor suppressor in other cancers. The role of caveolin-1 in colon carcinogenesis is controversial. We report here, for the first time, that caveolin-1 is transcriptionally induced in colon cancer cells in response to conditional expression of a full length adenomatous polyposis coli (APC) gene. This induction of caveolin-1 by APC is mediated by both FOXO1a, a member of the Forkhead family of transcription factor, and c-myc. The FOXO1a protein, which is increased by wild-type APC expression, induces caveolin-1 promoter-reporter activity and binds directly to a FKHR consensus binding sequence in the caveolin-1 promoter. The c-myc protein, which is reduced in the presence of wild-type APC, acts to repress caveolin-1 expression by acting at non-E-box containing elements in the caveolin-1 promoter. These data predict that caveolin-1 protein expression would be decreased early in colonic carcinogenesis, which is associated with loss of wild-type APC. Our results would be consistent with the interpretation that caveolin-1 may have tumor suppressing functions during early stages of colon carcinogenesis.
Roy
Upal K Basu
UK
Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona, USA.
Henkhaus
Rebecca S
RS
Ignatenko
Natalia A
NA
Mora
Jessica
J
Fultz
Kimberly E
KE
Gerner
Eugene W
EW
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*
D051242:Caveolin 1; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D016271:Proto-Oncogene Proteins c-myc