PMID:23418309

Citation	Wang, Y, He, X, Yu, Q and Eng, C' (2013) Androgen receptor-induced tumor suppressor, KLLN, inhibits breast cancer growth and transcriptionally activates p53/p73-mediated apoptosis in breast carcinomas. Hum. Mol. Genet. '
Abstract	Androgen receptor (AR) expression by immunohistochemistry correlates with better prognosis and survival among breast cancer patients. We and others have shown that AR inhibits proliferation and induces apoptosis in breast cancer cells. However, the mechanism of AR's anti-tumor effect in breast cancer is still not fully understood. Our recent study indicates that AR upregulates expression of tumor suppressor gene PTEN by promoter activation in breast cancer. KLLN, encoding KLLN protein, is a newly identified gene, which shares a bidirectional promoter with PTEN and is transcribed in the opposite direction. 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. After analyzing 188 normal breast and 1247 malignant breast cancer tissues, we observed 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 TP53 and TP73, with consequent elevated apoptosis and cell cycle arrest in breast cancer cells. We demonstrate, in vitro and in murine xenograph models, that both KLLN and PTEN are AR-target genes, mediating androgen-induced growth inhibition and apoptosis in breast cancer cells. Our observations suggest that KLLN might be used as a potential prognostic marker and novel therapy target for breast carcinomas.
Links	PubMed Online version:10.1093/hmg/ddt077
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:KILIN		GO:0006917: induction of apoptosis	ECO:0000315:		P		Fig 3 shows that KLLN induces apoptosis in cancer cells through transcriptional activation of p53 and p73.	complete CACAO 6639
HUMAN:KILIN		GO:0045786: negative regulation of cell cycle	ECO:0000314: direct assay evidence used in manual assertion		P		Fig 3 shows that transient transfection of KLLN in two breast cancer cell lines induces cell cycle arrest at S-phase	complete CACAO 6809
HUMAN:KILIN	involved_in	GO:0006915: apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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