The Role of DNA Methyltransferase in the Progression of Breast Cancer to a Hormone Independent Phenotype
Abstract
Estrogen and progesterone and their receptors play major roles in the development and function of the mammary gland as well as in breast cancer biology and treatment. However, 25-30% of human breast cancers lack ER alpha and PR expression and respond poorly to hormonal treatment. Absence of ER alpha and PR expression is associated with lack of transcript, methylation of the CpG islands in the promoter regions of these genes, and increased DMT activity and DMT1 protein. The purpose of this proposal is to address the hypothesis that specific inhibition of DMT1 by antisense oligoucleotides (DMT1 ASO) is sufficient to re-express ER and PR genes in ER-/PR-human breast cancer cell lines. Our results demonstrated that after DMT1 ASO treatment, human breast cancer cell lines used in this study showed significant growth inhibition, DMT1 expression was blocked at protein level as well as at mRNA level. ER expression was observed after DMT1 ASO multiple treatment. The re-expression of PR and other breast cancer suppressing genes are currently under investigation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA391690
Entities
People
- Lan Yan
Organizations
- Johns Hopkins University