Prostate epithelium-derived Ets transcription factor mRNA is overexpressed in human breast tumors and is a candidate breast tumor marker and a breast tumor antigen.
Ghadersohi, A and Sood, A K
Clin. Cancer Res., 7: 2731-8 (2001)
2001
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PURPOSE: There is a need to identify novel breast tumor-associated molecules with a potential as diagnostic/prognostic markers of breast cancer as well as targets of vaccine and drug discovery against this cancer. EXPERIMENTAL DESIGN: We used a combination of digital differential display and reverse transcription-PCR (RT-PCR) methods to identify breast tumor-associated cDNAs. RESULTS: It was found that prostate epithelium-derived Ets transcription factor (PDEF) and five other cDNAs occur at high frequency in the cDNA libraries from normal human breast tissue and human breast tumors. In contrast, these cDNAs are either undetectable or present at low frequencies in the cDNA libraries from other normal human tissues. RT-PCR expression analysis of PDEF showed it to be overexpressed in 14 of 20 primary human breast tumors and in one metastases tested. Also, consistent with the digital differential display data, RT-PCR analysis of PDEF expression showed highly restricted expression in normal human tissues. Furthermore, we show that PDEF transcript levels are 192-fold higher in the peripheral blood of a breast cancer patient in comparison with two normal individuals and another breast cancer patient. In contrast to PDEF, RT-PCR analysis of the expression of the other three cDNAs, including MYL5, Hs.44017, and Hs.215937, showed that these cDNAs are expressed in several normal human tissues. CONCLUSIONS: These results suggest that PDEF is a breast tumor-associated cDNA and should be further evaluated for its potential as a breast tumor marker and a breast tumor antigen. | 11555586
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PDEF, a novel prostate epithelium-specific ets transcription factor, interacts with the androgen receptor and activates prostate-specific antigen gene expression.
Oettgen, P, et al.
J. Biol. Chem., 275: 1216-25 (2000)
2000
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Prostate cancer, the most frequent solid cancer in older men, is a leading cause of cancer deaths. Although proliferation and differentiation of normal prostate epithelia and the initial growth of prostate cancer cells are androgen-dependent, prostate cancers ultimately become androgen-independent and refractory to hormone therapy. The prostate-specific antigen (PSA) gene has been widely used as a diagnostic indicator for androgen-dependent and -independent prostate cancer. Androgen-induced and prostate epithelium-specific PSA expression is regulated by a proximal promoter and an upstream enhancer via several androgen receptor binding sites. However, little progress has been made in identifying androgen-independent regulatory elements involved in PSA gene regulation. We report the isolation of a novel, prostate epithelium-specific Ets transcription factor, PDEF (prostate-derived Ets factor), that among the Ets family uniquely prefers binding to a GGAT rather than a GGAA core. PDEF acts as an androgen-independent transcriptional activator of the PSA promoter. PDEF also directly interacts with the DNA binding domain of androgen receptor and enhances androgen-mediated activation of the PSA promoter. Our results, as well as the critical roles of other Ets factors in cellular differentiation and tumorigenesis, strongly suggest that PDEF is an important regulator of prostate gland and/or prostate cancer development. | 10625666
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