Induction of Huntington Protein as a Novel Strategy for Prevention and Treatment of Breast Cancer

摘要

The objective of this study was to determine the role of the Huntingtin network genes in the progression of breast cancer. HAP1, HIP1 and HTT expression, DNA methylation status and histone acetylation of HAP1, HIP1 and HTT promoters were determined. HAP1 gene was silenced in breast cancer cell lines and in much lower extent in immortalized MCF10A cells, but not in normal human mammary epithelial cell line (HMEC). HAP1 expression was also dramatically reduced in breast tumors and adjacent normal breast tissues, compared with normal breast tissues of healthy women. Epigenetic analysis showed that HAP1, but not HTT or HIP1, had promoter DNA hypermethylation in breast cancer cell lines versus HMEC, and in breast cancer and adjacent normal breast tissues of patients versus normal controls. Further experiments using HTT and HAP-1 expressing plasmids in vitro showed that cell growth rate is significantly reduced in cancer cell lines. The results support that HTT and especially HAP1 may play functional roles in breast cancer development and progression. More importantly, HAP1 may have a protective role against breast cells from neoplastic transformation.