Identification of integrin ß6 gene promoter and analysis of its transcription regulation in colon cancer cells.

BACKGROUND: The integrin ß6 gene, which is expressed in epithelial cancer, plays a pivotal role in various aspects of cancer progression. The present research for integrin ß6 regulation mainly focuses on the post-transcription and translation related regulation mechanism and its role in tumorigenesis. The mechanisms of how the integrin ß6 gene is regulated transcriptionally, and the promoter and transcription factors responsible for basic transcription of integrin ß6 gene remain unknown. AIM: To clone and characterize the integrin ß6 promoter. METHODS: Software analysis was used to predict the region of integrin ß6 promoter. Luciferase reporter plasmids, which contained the integrin ß6 promoter, were constructed. Element deletion analysis was performed to identify the location of core promoter and binding sites for transcription factors. RESULTS: The regulatory elements for the transcription of the integrin ß6 gene were located between -286 and -85 and contained binding sites for transcription factors such as STAT3 and Ets-1. CONCLUSION: For the first time, we found the region of ß6 core promoter and demonstrated the binding sites for transcription factors such as Ets-1 and STAT3, which are important for integrin ß6 promoter transcription activity. These findings are important for investigating the mechanism of integrin ß6 activation in cancer progression.

Prognostic impact of KRAS and BRAF mutations in patients who underwent simultaneous resection for initially resectable colorectal liver metastases.

This study aimed to explore the prognostic impact of KRAS and BRAF mutations in patients who underwent simultaneous resection for synchronous colorectal liver metastases (SCRLMs) that were initially resectable. Clinicopathological and outcome data of 139 consecutive patients with SCRLMs who underwent resection between July 2003 and July 2013 was collected from our prospectively established SCRLM database. The KRAS and BRAF genotypes were evaluated in the primary cancer tissues by pyrosequencing. The prognostic value of KRAS and BRAF status was assessed by Kaplan-Meier and Cox regression analyses. KRAS and BRAF mutated in 28.8% and 7.2% of the patients with SCRLMs, respectively, but the genotypes did not significantly associate with any clinicopathologic characteristics. By Kaplan-Meier survival analysis, we found KRAS mutation was not significantly associated with short overall survival (OS) (P = 0.213), but was significantly correlated with short disease-free survival (DFS) (P = 0.041); BRAF mutation was significantly associated with both short OS and DFS (P = 0.001, P<0.001, respectively). Multivariate survival analysis showed KRAS mutation was an independent negative prognostic factor for DFS (P = 0.005) and BRAF mutation was an independent negative prognostic factor for OS and DFS (P = 0.001, P<0.001, respectively). KRAS and BRAF mutation similarly contributed to an adverse prognostic effect in patients who underwent simultaneous resection for SCRLMs that were initially resectable. These findings should suggest the use of KRAS and BRAF status in current practice as an important determinant for precision surgery for initially resectable SCRLMs.