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Smad4 Expression (smad4 + expression)
Selected AbstractsThe role of SMAD4 in early-onset colorectal cancerCOLORECTAL DISEASE, Issue 3 2010S. G. Royce Abstract Objective, Chromosomal loss within the region of 18q and loss of SMAD4 expression have been reported to be frequent somatic events during colorectal cancer tumour progression; however, their associations with age at onset have not been widely studied. Method, We analysed 109 tumours from a population-based case-family study based on colorectal cancers diagnosed before the age of 45 years. These patients with early-onset colorectal cancer had been previously screened for germ-line mismatch repair gene mutations, microsatellite instability (that included the mononucleotide repeat in TGF,RII) and somatic k-ras mutations. We measured SMAD4 protein expression using immunohistochemistry and SMAD4 copy number using quantitative real-time PCR. Results, Loss of SMAD4 protein expression was observed in 27/109 (25%) of cancers tested and was more commonly observed in rectal tumours (15/41, 36%) when compared with tumours arising in the colon (11/66, 17%) (P = 0.04). There was no association between SMAD4 protein expression and TGF,R11 mutation status, SMAD4 copy number, family history, MSI status, tumour stage or grade. Conclusion, Loss of SMAD4 expression is a common feature of early-onset colorectal tumours as it is in colorectal cancers diagnosed in other age-groups. Taken together, the molecular pathways (genetic and epigenetic) now known to be involved in early-onset colorectal cancer only explain a small proportion of the disease and require further exploration. [source] Loss of BMP2, Smad8, and Smad4 expression in prostate cancer progression,THE PROSTATE, Issue 3 2004Lisa G. Horvath Abstract BACKGROUND The role of the bone morphogenetic protein (BMP) pathway in prostate cancer (PC) is unclear. This study aimed to characterize aspects of the BMP pathway in PC by assessing BMP2, Smad8, and Smad4 expression in normal, hyperplastic, and malignant prostate tissue, and to correlate findings with progression to PC. METHODS Radical prostatectomy (RP) specimens from 74 patients with clinically localized PC (median follow-up 51 months, range 15,152), 44 benign prostatic hypertrophy (BPH) lesions, and 4 normal prostates (NPs) were assessed for BMP2, Smad8, and Smad4 expression using immunohistochemistry. RESULTS Both BMP2 (P,<,0.001) and nuclear Smad4 (P,<,0.0001) expression were significantly decreased in PC compared to benign prostate tissue. Nuclear Smad8 was present in normal/benign prostate tissue but absent in PC and adjacent hyperplasia. Furthermore, loss of BMP2 (P,<,0.001) and decreased nuclear Smad4 (P,=,0.05) expression correlated with increasing Gleason score. CONCLUSIONS These data suggest that decreased BMP2, nuclear smad8 and nuclear Smad4 expression are associated with the progression to PC, and in particular loss of BMP2 and Smad4 are related to progression to a more aggressive phenotype. © 2004 Wiley-Liss, Inc. [source] Promoter-wide analysis of Smad4 binding sites in human epithelial cellsCANCER SCIENCE, Issue 11 2009Daizo Koinuma Smad4, the common partner Smad, is a key molecule in transforming growth factor-, (TGF-,) family signaling. Loss of Smad4 expression is found in several types of cancer, including pancreatic cancer and colon cancer, and is related to carcinogenesis. Here we identified Smad4 binding sites in the promoter regions of over 25 500 known genes by chromatin immunoprecipitation on a microarray (ChIP-chip) in HaCaT human keratinocytes. We identified 925 significant Smad4 binding sites. Approximately half of the identified sites overlapped the binding regions of Smad2 and Smad3 (Smad2/3, receptor-regulated Smads in TGF-, signaling), while the rest of the regions appeared dominantly occupied by Smad4 even when a different identification threshold for Smad2/3 binding regions was used. Distribution analysis showed that Smad4 was found in the regions relatively distant from the transcription start sites, while Smad2/3 binding regions were more often present near the transcription start sites. Motif analysis also revealed that activator protein 1 (AP-1) sites were especially enriched in the sites common to Smad2/3 and Smad4 binding regions. In contrast, GC-rich motifs were enriched in Smad4-dominant binding regions. We further determined putative target genes of Smad4 whose expression was regulated by TGF-,. Our findings revealed some general characteristics of Smad4 binding regions, and provide resources for examining the role of Smad4 in epithelial cells and cancer pathogenesis. (Cancer Sci 2009) [source] | ||||||||||