The results suggest that genetic and epigenetic alteration of KLF6 may play a minor role in the development of HCC.

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Ras proteins control signaling pathways that are key regulators of several aspects of normal cell growth and malignant transformation. BRAF, which encodes a RAF family member in the downstream pathway of RAS, is somatically mutated in a number of human cancers. The activating mutation of BRAF is known to play a role in tumor development. As there have been no data on the BRAF mutation in stomach cancer, we analysed the genomic DNAs from 319 stomach carcinomas for the detection of somatic mutations of BRAF. Overall, we detected BRAF mutations in seven stomach carcinomas (2.2%). Five of the seven BRAF mutations involved Val 599, the previously identified hotspot, but the substituted amino acid (V599 M) was different from the most common BRAF mutation (V599E). The remaining two mutations involved a conserved amino acid (D593G). One tumor had both BRAF and KRAS mutations. This is the first report on BRAF mutation in stomach cancer, and the data indicate that BRAF is occasionally mutated in stomach cancer, and suggest that alterations of RAS pathway both by RAS and BRAF mutations contribute to the pathogenesis of stomach cancer.

The p34SEI-1 protein exerts oncogenic effects via regulation of the cell cycle, which occurs through a direct interaction with cyclin-dependent kinase 4. Such regulation can increase the survival of various types of tumor cells. Here, we show that the antiapoptotic function of p34 SEI-1 increases tumor cell survival by protecting the X-linked inhibitor of apoptosis protein (XIAP) from degradation. Our findings show that p34 inhibits apoptosis. This antiapoptotic effect was eliminated by the suppression of p34 SEI-1 expression. We also determined that direct binding of p34 SEI-1 to the BIR2 domain prevents ubiquitination of XIAP. Interestingly, p34SEI-1 expression is absent or weak in normal tissues but is strongly expressed in tissues obtained from patients with breast cancer. Furthermore, the expression levels of p34 SEI-1 and XIAP seem to be coordinated in human breast cancer cell lines and tumor tissues. Thus, our findings reveal that p34 SEI-1 uses a novel apoptosis-inhibiting mechanism to stabilize XIAP. [Cancer Res 2009;69(3):741-6]