Expression of maspin in prostate cells is regulated by a positive ets element and a negative hormonal responsive element site recognized by androgen receptor.
Prostate cancer is the most common cancer in men. The molecular mechanisms leading to its development are poorly understood. Maspin is a tumor-suppressing serpin expressed in normal breast and prostate epithelium. We have found that expression of maspin in normal and carcinoma-derived prostate epithelial cells is differentially regulated at the transcriptional level. We have identified two different kinds of cis elements, Ets and hormonal responsive element (HRE), in the maspin promoter. The Ets element is active in regulating maspin expression in normal prostate epithelial cells but inactive in tumor cells. The HRE site is a negative element that is active in both cell types. This negative DNA sequence can repress a heterologous promoter recognized by the androgen receptor. We conclude that expression of maspin is under the influence of both a positive Ets and a negative HRE element. Loss of maspin expression during tumor progression apparently results from both the absence of transactivation through the Ets element and the presence of transcription repression through the negative HRE element recognized by androgen receptor.
Zhang
M
M
Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Magit
D
D
Sager
R
R
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004848:Epithelium; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D011944:Receptors, Androgen / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015842:Serine Proteinase Inhibitors / Q000096:biosynthesis; D015843:Serpins / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; C085344:SERPIN-B5; D015842:Serine Proteinase Inhibitors; D015843:Serpins; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase