BackgroundCoactivator-associated arginine methyltransferase 1 (CARM1) functions as a transcriptional coactivator of androgen receptor (AR)-mediated signaling. Correspondingly, overexpression of CARM1 has been associated with the development of prostate cancer (PCa) and its progression to androgen-independent PCa. In our preliminary study, however, the promoting effects of CARM1, with regard to androgen-stimulated AR target gene expression were minimal. These results suggested that the AR target gene expression associated with CARM1 may result primarily from non-hormone dependent activity. The goal of this study was to confirm the pattern of expression of CARM1 in human tumors and determine the mechanism of action in CARM1 overexpressed tumors.MethodsTissue microarray was used to determine the pattern of expression of CARM1 in human cancers by immunohistochemistry. CARM1 expression was also evaluated in prostate and colorectal surgical specimens and the clinical records of all cases were reviewed. In addition, a reporter transcription assay using the prostate-specific antigen (PSA) promoter was used to identify the signaling pathways involved in non-hormone-mediated signal activation associated with CARM1.ResultsThe tissue microarray showed that CARM1 was particularly overexpressed in the colorectal cancers while CARM1 expression was not prevalent in the prostate and breast cancers. Further studies using surgical specimens demonstrated that CARM1 was highly overexpressed in 75% of colorectal cancers (49 out of 65) but not in the androgen-independent PCa. In addition, CARM1's coactivating effect on the entire PSA promoter was very limited in both androgen-dependent and androgen-independent PCa cells. These results suggest that there are other factors associated with CARM1 expression in PSA regulation. Indeed, CARM1 significantly regulated both p53 and NF-κB target gene transcription.ConclusionsThe results of this study suggest that, in addition to its role in activation of steroid receptors, CARM1 functions as a transcriptional modulator by altering the activity of many transcriptional factors, especially with regard to androgen independent PCa and colorectal cancers.

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Objective:The aim of the present study was to investigate the relationship between diabetes mellitus (DM) and tumor features in patients with non-muscle invasive bladder cancer (NMIBC). Methods: Data from 251 patients who underwent transurethral resection (TUR) for NMIBC from January 2000 to June 2010 were analyzed retrospectively. Patients were divided into two groups: Group I, 159 patients (63%) who did not have DM at the time of surgery; and (ii) Group II, 92 patients (37%) who had DM at the time of surgery. Recurrence-and progression-free survival was assessed in both groups. Preoperative HbA1c levels, as parameter of glycemic control, were determined in Group II patients, with patients divided into two subgroups: (i) HbA1c Ն7.0%; and (ii) HbA1c <7.0%. The clinical features of the bladder tumor were compared in these two subgroups. Results: Compared with Group I, Group II patients were older and had a higher rate of hypertension, recurrence, and progression (P < 0.05). Univariate survival analysis showed that gender, DM, smoking, and serum creatinine were associated with recurrence-free survival (P < 0.05), whereas DM, stage, grade, intravesical instillation, and serum creatinine were associated with progression-free survival. In multivariate survival analysis, DM was found to be an independent factor for recurrence-(hazard ratio [HR] 2.11; 95% confidence interval [CI] 1.4-3.2; P = 0.001) and progression-free survival (HR 9.35; 95% CI 3.1-28.6; P = 0.001). Furthermore, patients with HbA1c Ն7.0% exhibited a significantly higher rate of multiplicity (P = 0.001), tumor grade (P = 0.03), and intravesical treatment (P = 0.04). Conclusions: In conclusion, DM seems to be an independent predictor of recurrence-and progression-free survival in NMIBC patients. Further prospective studies are needed to establish the prognostic significance of postoperative glycemic control in this patient population.