Access Type

Open Access Dissertation

Date of Award

January 2017

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Cancer Biology

First Advisor

Manohar Ratnam

Abstract

ABSTRACT

MECHANISMS OF HORMONAL REGULATION OF INVASIVENESS AND METASTASIS OF LUMINAL BREAST CANCER

By

THOMAS MCFALL

December 2017

Advisor: Dr. Manohar Ratnam

Major: Cancer Biology

Degree: Doctor of Philosophy

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.

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