Androgen regulation of the cell-cell adhesion molecule-1 (Ceacam1) gene.
Previous studies have established that the cell-cell adhesion molecule-1 (CEACAM1, previously known as C-CAM1) functions as a tumor suppressor in prostate cancer and is involved in the regulation of prostate growth and differentiation. However, the molecular mechanism that modulates CEACAM1 expression in the prostate is not well defined. Since the growth of prostate epithelial cells is androgen-regulated, we investigated the effects of androgen and the androgen receptor (AR) on CEACAM1 expression. Transient transfection experiments showed that the AR can enhance the Ceacam1 promoter activity in 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-promoter binding because a mutant AR defective in DNA binding failed to upregulate reporter gene expression. Furthermore, electrophoretic mobility shift assays demonstrated that the AR specifically binds to this sequence, and mutation analysis of the potential ARE sequences revealed a region within the sequence that was required for the AR to activate the Ceacam1 gene. Therefore, the regulation of Ceacam1 gene expression by androgen may be one of the mechanisms by which androgen regulates prostatic function.
Phan
D
D
Department of Molecular Pathology, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Sui
X
X
Chen
D T
DT
Najjar
S M
SM
Jenster
G
G
Lin
S H
SH
D000728:Androgens / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000235:genetics*; D000943:Antigens, Differentiation / Q000187:drug effects / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014162:Transfection
D000728:Androgens; D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D011944:Receptors, Androgen