Earlier studies also suggest that androgens could induce apoptosis in breast cancer cells (4,5).Thus far, the mechanism of how androgens suppress proliferation and induces apoptosis in breast cancer is still not fully understood.To begin to explore the role KLLN plays in human breast carcinomas, and to determine patient relevance, we first used publicly available databases to perform expression between normal breast and breast cancer tissues.A search through the Gene Expression Omnibus identified 156 normal breast and 1070 breast carcinoma tissue samples. 1D, lower-left) and IDC show loss of KLLN expression in both stroma and epithelium ( and Fig. Our findings suggest that loss of KLLN in the epithelium is an early event in breast cancer development, and loss of KLLN expression in stroma is perhaps a later event during tumor progression.After analyzing 188 normal breast and 1247 malignant breast cancer tissues, we observed the loss of KLLN in multiple breast cancer subtypes and this decreased KLLN expression associates with tumor progression and increasing histological grade in invasive carcinomas.We characterize KLLN, for the first time, as a transcription factor, directly promoting the expression of are AR-target genes, mediating androgen-induced growth inhibition and apoptosis in breast cancer cells.Empty vector/scrambled si RNA were used as control for KLLN overexpression/knockdown, and these two controls showed the same growth rate.
To investigate the mechanism of KLLN's anti-tumorigenic effect, we first examined its function on the cell cycle.So far, the function of KLLN has never been studied in tumorigenesis.Here, we define KLLN as a tumor suppressor in breast carcinomas, which inhibits tumor growth and invasiveness.A total of 68 normal breast tissues, 822 primary IDC and 393 metastatic tumor samples were In order to further elucidate the role that KLLN plays in breast carcinogenesis, we surveyed KLLN protein expression in 10 breast cancer cell lines.We found that MCF-7, MDA-MB-453, BT20 and SKBR3 cells express KLLN protein, while the rest of the breast cancer cell lines do not have detectable KLLN (Fig. Immunofluorescence staining and subcellular fractionation clearly show KLLN's nuclear localization, suggesting its active role in the breast cancer cell nuclei (Fig.
However, the mechanism of AR's anti-tumor effect in breast cancer is still not fully understood.