Wild-type APC regulates caveolin-1 expression in human colon adenocarcinoma cell lines via FOXO1a and C-myc
✍ Scribed by Upal K. Basu Roy; Rebecca S. Henkhaus; Natalia A. Ignatenko; Jessica Mora; Kimberly E. Fultz; Eugene W. Gerner
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- English
- Weight
- 231 KB
- Volume
- 47
- Category
- Article
- ISSN
- 0899-1987
- DOI
- 10.1002/mc.20451
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✦ Synopsis
Abstract
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. © 2008 Wiley‐Liss, Inc.