TMEFF2: A Novel Gene Expressed Selectively in Androgen-Responsive Prostate Cancers
Annual summary rept. 1 Mar 2002-28 Feb 2003
CEDARS-SINAI MEDICAL CENTER LOS ANGELESCA
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TMEFF2 is a novel transmembrane protein-containing two follistatin domains and an epidermal growth factor-like motif-that is mainly expressed in the prostate and brain. TMEFF2 is highly expressed in the AD prostate cancer cell line, LNCaP, and is controlled by androgen. TMEFF2 is also upregulated by estrogen in a dose- and time-dependent manner. Ectopic expression of TMEFF2 can inhibit prostate cancer cell growth. I cloned the 5- flanking region of the human TMEFF2 gene and using a luciferase reporter assay showed that it contains a functional promoter. The 0.7-kb region upstream to the TMEFF2 transcription start site encompasses the minimal promoter required for TMEFF2 expression. Sequence analysis of the TMEFF2 promoter revealed potential binding sites for several transcription factors including Spl and an E-box that could be recognized by c-Myc. An inverse correlation between TMEFF2 and c-Myc expression was found in CWR22 prostate xenografts. Reporter gene and mobility shift as says demonstrated that c-Myc could repress TMEFF2 gene expression through its cognate site. In light of the probable role of TMEFF2 in inhibiting cell growth, its suppression may contribute to the oncogenic properties of c-Myc.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research