Androgen regulation of the cell-cell adhesion molecule-1 (Ceacam 1) gene

Previous studies have established that the cell-cell adhesion molecule-1 (C EACAM1, previously known as C-CAM1) functions as a tumor suppressor in pros tate cancer and is involved in the regulation of prostate growth and differ entiation. However, the molecular mechanism that modulates CEACAM1 expressi on in the prostate is not well defined. Since the growth of prostate epithe lial cells is androgen-regulated, we investigated the effects of androgen a nd the androgen receptor (AR) on CEACAM1 expression. Transient transfection experiments showed that the AR can enhance the Ceacam1 promoter activity i n a ligand-dependent manner and that the regulatory element resides within a relatively short (- 249 to - 194 bp) segment of the 5'-flanking region of the Ceacam1 gene. This androgen regulation is likely through direct AR-pro moter binding because a mutant AR defective in DNA binding failed to upregu late reporter gene expression. Furthermore. electrophoretic mobility shift assays demonstrated that the AR specifically binds to this sequence, and mu tation analysis of the potential ARE sequences revealed a region within the sequence that was required for the AR to activate the Ceacam1 gene. Theref ore, the regulation of Ceacam1 gene expression by androgen may be one of th e mechanisms by which androgen regulates prostatic function. (C) 2001 Elsev ier Science Ireland Ltd. All rights reserved.