Specific Transcription Factors Prognostic for Prostate Cancer

We have previously identified (M. Wang et aL, OncoL Res., in press, 1998) an enhancer element [human tissue inhibitor of metalloproteinase-1 enhancer-i (HTE)] for the human tissue inhibitor of metalloproteinase-1 promoter that binds a novel zinc finger, cysteine-rich transcription factor (CRTF). In this study, we have used electrophoretic mobifity shift assays to examine the relative level of expression of CRTF, jun/fos, and IFN-’y responsive signal transducer activators of transcription (STATs) that bind specific HTE, activator protein, and IFN-’y (Fc’y and interferon regulatory factor) response motifs in tumor lines and human prostate tissue [Le., normal (n = 3); benign prostatic hyperplasia (BPH; n = 12); high grade prostate intraepithelial neoplasia (PIN; a = 10); and prostate cancer adenocarcinoma (PCA; n = 61) plus seminal vesicle (n = 10) tissues]. The data showed that CRTF was 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, jun/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 organconfined specimens but at significantly elevated levels (P < 0.001) in samples exhibiting capsular penetration and localisNi spread, which indicated that CRTF and perhaps jun/fos were markers for cancer progression.