r development. Reduced NLK expression was closely MedChemExpress Mertansine associated with the breast cancer malignancy. Malignant transformation is a complex process that may be regulated, at least in part, by reduced expression of NLK. We found a statistically significant correlation between the expression of NLK and c-Myb. Furthermore, we observed an inverse correlation between NLK and c-Myb expression in breast carcinomas, with low NLK expression being a poor prognostic factor. The negative correlation between NLK and c-Myb expression was also observed in normal human breast epithelial and breast cancer cell lines, regardless of estrogen receptor expression status. Taken together, our observations supported the hypothesis that NLK might contribute to the progression of breast carcinoma as a regulator of c-Myb. In our study, the cause of growth suppression in the breast cells by wild-type NLK could be either cell cycle arrest, increased apoptosis rate or both. The overexpression of NLK resulted 17266205 in suppressed cell growth and an arrest in the cell cycle transition. These findings suggest that overexpression of NLK might act as an inhibitor of breast cancer cell proliferation by blocking cell growth. Previous studies have suggested that NLK overexpression induced apoptosis in human colon cancer cells. Our flow cytometry data, as well as the nuclear condensation and fragmentation phenotype observed using microscopy, indicated that NLK expression increased the number of apoptotic cells. The present study showed that induction of wild-type NLK in the human breast carcinoma cell line MCF-7 caused cell growth suppression and apoptosis induction. c-myc is a target of c-Myb, and activation of the c-myc gene is required for Myb-mediated transformation. Bcl-2 is a direct target gene of the protooncogene c-Myb. Several studies have shown that c-Myb regulates bcl-2 gene expression in hematopoietic cells. Bcl-2 expression is reduced and apoptosis is increased in the colonic epithelium of embryos with a disrupted cmyb gene. In our study, c-Myb expression was induced from late G1 to S phase, whereas NLK was decreased simultaneously with the accumulation of c-Myb. We also found that cMyb expression was significantly decreased by NLK overexpression, resulting in lower levels of c-myc and bcl-2 in MCF-7 cells. We hypothesize that NLK might be involved in the degradation of c-Myb and that its target genes c-myc and bcl-2 might be potential prognostic factors for breast carcinoma. The underlying mechanism by which NLK regulates c-Myb expression remains to be elucidated; however, NLK’s role in human breast cancer development and progression by attenuating c-Myb activity makes it an attractive target for cancer therapy. Other than the NLK/c-Myb pathway, additional mitogenic cascades 
have been found to be associated with NLK function in cancer. Jun Yasuda proposed that NLK might function as a tumor suppressor in colon cancer by inhibiting the Wnt/b-catenin pathway, which suppresses the transcriptional activity of the bcatenin/T-cell factor complex by phosphorylating TCF. More studies are needed to address the possibility of other pathways regulating NLK function in breast cancer cells, which has been reported previously for other cell lines. Proliferation and Apoptosis in Breast Cancer This study demonstrates the consequences of NLK dysregulation in human breast carcinoma. The overexpression of NLK suppressed tumor cell proliferation and transforming 9521749 potential via the transcriptiona
