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Mechanisms of Hormonal Regulation of Invasiveness and Metastasis of Luminal Breast Cancer
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Mechanisms of Hormonal Regulation of Invasiveness and Metastasis of Luminal Breast Cancer
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Dissertation
Mechanisms of Hormonal Regulation of Invasiveness and Metastasis of Luminal Breast Cancer
2017
Overview
Over 20% of breast cancer cases present with distal metastasis and they are predominantly of luminal subtypes. As luminal breast cancer is relatively indolent, it is believed that progression to metastasis must occur over many years, generally well into post-menopausal years. Unfortunately, very little is known about the mechanisms by which these hormone receptor positive tumors metastasize, likely in part due to their slow metastatic rates in animal model systems as well. Moreover, the literature lacks adequate mechanistic understanding of cross talk between estradiol (E2) and progesterone, particularly in the context of breast cancer invasion and metastasis. In this thesis, we sought to investigate the roles of estrogen and progesterone and their nuclear receptors to better understand hormonal regulation of metastasis at physiologically relevant hormone levels both pre- and post-menopause. The novelty of our experimental approach and study design is three-fold: 1. exploration of the isoform-specific actions of the progesterone receptor; 2. investigation of selective micro RNA mediated pathways of cross talk between estrogen and progesterone and 3. development of a quantitative lymph node infiltration assay to monitor metastasis of luminal breast cancer in xenograft models.
