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(14 of 32) of the Grade 2 tumors, and 82% (23 of 28) of the Grade 3 tumors were diagnosed by cytology. All five patients with carcinoma in situ were positive for cytology as well as for telomerase activity. When cytology was compared with the Preliminary data for this article was presented PCR-based telomerase assay in determining the presence of bladder carcinoma, in abstract form during the 1997 Annual Meetthe difference in the overall detection rates (85% for telomerase vs. 51% for cytoling of the American Urological Association.ogy) was significant (P õ 0.001). Furthermore, when telomerase activity was compared with cytology for low grade lesions (Grades 1 and 2), the difference in the The authors acknowledge the technical assisdetection rates (82% for telomerase vs. 31% for cytology) was also significant tance of Wei-Ping Shu, which involved running (P õ 0.001). some of the initial telomerase assays.CONCLUSIONS. Urinary cytology yields poor results for low grade tumors. This

Androgen receptor (AR) plays an important role in normal prostate function as well as in the etiology of prostate cancer. Activation of AR is dictated by hormone binding and by interactions with coregulators. Several of these coregulators are known targets of Ras-related signals. Recent evidence suggests that Ras activation may play a causal role in the progression of prostate cancer toward a more malignant and hormone-insensitive phenotype. In the present study, we used a transcription factor-transcription factor interaction array method to identify the zinc finger protein Ras-responsive element binding protein (RREB-1) as a partner and coregulator of AR. In LNCaP prostate cancer cells, RREB-1 was found to be present in a complex with endogenous AR as determined by coimmunoprecipitation, glutathione S-transferase pull down, and immunofluorescence analyses. RREB-1 bound to the prostate-specific antigen (PSA) promoter as assessed by chromatin immunoprecipitation. Transient expression of RREB-1 down-regulated AR-mediated promoter activity and suppressed expression of PSA protein. The repressor activity of RREB-1 was significantly attenuated by cotransfection of activated Ras. Moreover, expression of the dominant-negative N-17-Ras or, alternatively, use of the MAPK kinase inhibitor PD98059 [2-(2-amino-3-methyoxyphenyl)-4H-1-benzopyran-4-one] abolished the effect of Ras in attenuating RREB-1-mediated repression. Furthermore, inhibition of RREB-1 expression by RNA interference enhanced the effect of Ras on PSA promoter activity and PSA expression. In addition, activation of the Ras pathway depleted AR from the RREB-1/AR complex. Collectively, our data for the first time identify RREB-1 as a repressor of AR and further implicate the Ras/MAPK kinase pathway as a likely antagonist of the inhibitory effects of RREB-1 on androgenic signaling.

BACKGROUND The advent of the prostate‐specific antigen (PSA) test has had a profound impact on the diagnosis and treatment of prostate carcinoma. However, the use of PSA levels alone for screening for prostate carcinoma was compromised by the variations in the amount of PSA produced by the benign prostatic tissue specimens. Proteins were involved in various pathways that determine the behavior of a cell. Therefore, information regarding proteins may reveal drug targets and/or markers for early detection. METHODS The authors used surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry to determine the protein profiles from fresh tissues of the prostate. Laser capture microdissection was performed to isolate pure populations of cells. RESULTS The authors identified a protein with an average m/Z of 24,782.56 ± 107.27 that was correlated with the presence of prostate carcinoma. Furthermore, using laser capture microdissection, they demonstrated that the origin of this protein, which the authors designated PCa‐24, was derived from the epithelial cells of the prostate. PCa‐24 expression was detected in 16 of 17 (94%) prostate carcinoma specimens but not in paired normal cells. In addition, this protein was not expressed in any of the 12 benign prostatic hyperplasia specimens that were assayed. CONCLUSIONS PCa‐24 may be useful a marker for prostate carcinoma. Cancer 2003;98:2576–82. © 2003 American Cancer Society.