Abstract P1-04-07: The mRNA Expression of DAP1 in Human Breast Cancer: Correlation with Clinicopathological Parameters

Abstract

Abstract BACKGROUND: This pilot study is the first to focus on the potential role for death-associated protein 1 (DAP1) in human breast cancer. MATERIAL AND METHODS: mRNA expression of DAP1 in breast cancer tissues (n = 127) and normal background tissues (n = 33) were determined using quantitative polymerase chain reaction (qPCR) and correlated with clinicopathological data accumulated over a 10-year follow-up period. Furthermore the effects of DAP1 knockout in breast cancer cell lines were investigated. RESULTS: The expression of DAP1 mRNA was demonstrated to decrease with increasing Nottingham Prognostic Index (NPI2 vs. NPI3, p = 0.0026), and TNM stage (TNM1 vs. 4, p = 0.0039). Lower DAP1 expression levels were significantly associated with local recurrence (p = 0.02) and distant metastasis (p = 0.001). The knockout of the DAP1 gene in MCF-7 cell lines resulted in a significant decrease in the mRNA expression of P-21 and DELE compared with controls, p = 0.04). However, the knockout of DAP1 had no effect on the expression of caspase 8 and 9. CONCLUSIONS: This study demonstrates an inverse association between DAP1 mRNA levels and tumour stage and clinical outcome in breast cancer. This may be suggestive of a relationship between oncogenesis and the autophagy pathway meriting further investigation. These results also indicate that the pro-apoptotic function seems to be estrogen-dependent but independent of caspase 8 and 9. The DAP1 pro-apoptotic pathway may involve P-21 and DELE proteins. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-04-07.