Background: Coactivator-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.Methods: Tissue 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.Results: The 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.Conclusions: The 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.
Background. The aim of this study was to test the utility of our computed tomography (CT) grading system, compared with endoscopy, for association with the development of esophageal stricture in patients with caustic ingestion. Methods. This retrospective case series involved 49 patients with caustic ingestion from 1998 to 2009. The degree of esophageal damage was graded using a scoring system based on the extent of esophageal wall edema and the damage in adjacent tissue as seen on thoracoabdominal CT scans. The presence of esophageal stricture was established by esophagography. Diagnostic performance was compared using receiver operating characteristic (ROC) analysis. Sensitivity and specificity were calculated for the grading system. Results. The CT grading score results showed that grade III was the most common injury (20 cases, 40.8%), followed by grade IV (14 cases, 28.6%), grade II (9 cases, 18.4%), and grade I (6 cases, 12.2%). In addition, damage to the esophagus was significantly correlated with esophageal stricture when the extent of damage approached grades III and IV (p < 0.001). The CT grading system for esophageal stricture resulted in a slightly larger area under the receiver operating characteristic curve (0.90) compared with endoscopic grading system (0.79). The sensitivity and specificity of CT grading system were moderately higher than those of endoscopic grading system. Conclusion. Assessment of the degree of esophageal damage using CT, a noninvasive modality, in patients who visit the emergency department following caustic ingestion should be useful in estimating the occurrence of complications including esophageal stricture.