Accession Number : ADA615228


Title :   In Utero Estrogen Exposure Increases Antiestrogen Resistance by Inducing EMT


Descriptive Note : Annual rept. 15 Jan 2014-14 Jan 2015


Corporate Author : GEORGETOWN UNIV WASHINGTON DC


Personal Author(s) : Bouker, Kerrie B


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a615228.pdf


Report Date : Feb 2015


Pagination or Media Count : 13


Abstract : Endocrine therapies such as antiestrogens (AE) are widely used in estrogen receptor positive (ER+) breast cancer, due to their efficacy and limited toxicity. However, the clinical reality is that of the 50% of ER+ patients that initially respond to these therapies, many will acquire resistance and recur. The causes of antiestrogen resistance are currently unclear. Our recent preclinical study found that maternal exposure to excess estrogens during pregnancy increases the risk that AE resistance in ER+ mammary tumors in the offspring. This increase may be caused by epigenetic mechanisms, such as an increase in DNA methyltransferases (DNMT) and methylation, and histone deacetylases (HDAC) and histone modifications. In this study, our preliminary data show not only an increase in TAM resistance in rats exposed to in utero estrogen, but concurrent treatment with DNMT and HDAC inhibitors inhibited this resistance, suggesting that epigenetic changes driven by estrogenic exposures early in life may preprogram the breast to develop tumors with a higher propensity to develop antiestrogen resistance.


Descriptors :   *BREAST CANCER , *ESTROGENS , CLINICAL MEDICINE , DEOXYRIBONUCLEIC ACIDS , EMBRYOLOGY , ENDOCRINE GLANDS , FEMALES , GENETIC ENGINEERING , HISTONES , INHIBITORS , MAMMARY GLANDS , MODIFICATION , NEOPLASMS , PATIENTS , RESISTANCE , RISK , THERAPY , TOXICITY


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE