SPECIFIC TRANSCRIPTION FACTORS PROGNOSTIC FOR PROSTATE-CANCER PROGRESSION

We have previously identified jh I. Wang et at, Oncol, Res., in press, 1998) an enhancer element [human tissue inhibitor of metalloproteinas e-1 enhancer-1 (HTE)I for the human tissue inhibitor of metalloprotein ase-l promoter that binds a novel zinc finger, cysteine-rich transcrip tion factor (CRTF), In this study, me have used electrophoretic mobili ty shift assays to examine the relative level of expression of CRTF, j un/fos, and IFN-gamma responsive signal transducer activators of trans cription (STATs) that bind specific HTE, activator protein, and IFN-ga mma (Fc gamma and interferon regulatory factor) response motifs in tum or lines and human prostate tissue Ei,e,, normal (n = 3); benign prost atic hyperplasia (BPH; n = 12); high grade prostate intraepithelial ne oplasia (PIN; n = 10); and prostate cancer adenocarcinoma (PCA; n = 61 ) plus seminal vesicle (n = 10) tissues], The data showed that CRTF wa s overexpressed in PCA (Gleason's score, 10>8>6>5>4) compared with BPH , PIN, seminal vesicle, and normal tissues. To a much lesser degree, j un/fos and STAT 1 were also elevated in PCA compared to BPH, PIN, and normal tissues. In addition, blinded studies showed that CRTF and jun/ fos were present at low levels in organ-confined specimens but at sign ificantly elevated levels (P < 0.001) in samples exhibiting capsular p enetration and localized spread, which indicated that CRTF and perhaps jun/fos were markers for cancer progression.