Theses
Date of Award
Spring 5-28-2026
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biological Sciences
First Advisor
Rebeca San Martin
Second Advisor
Kristina Ames
Abstract
Prostate cancer is accompanied by a reactive stroma (RS) response, characterized by aggregation of cancer-associated fibroblasts (CAF). RS is orchestrated by epithelial production of transforming growth factor beta (TGFβ), which induces tissue-resident prostate mesenchymal stem cells (trMSCs) to differentiate into myofibroblasts and cancer-associated fibroblasts (CAFs). These cells remodel the microenvironment by producing extracellular matrix proteins and soluble signals that promote cell proliferation. Our preliminary studies showed that reactive stroma myofibroblasts produce the hormone prolactin (PRL). This in vitro RS model showed an increased amyloid precursor protein (APP) expression in myofibroblast-adjacent epithelial cells. APP is a protein primarily known for its role in the development of Alzheimer’s disease: it decorates the cell surface, where it is processed into lower molecular weight peptides by the protease action of Beta secretases 1 and 2 (BACE1 and BACE2). Epidemiological studies have linked a higher incidence of Alzheimer’s disease in patients exposed to androgen ablation, suggesting that the absence of testosterone plays a role in the deposition of abnormal levels of amyloid peptides. We propose that exposure to reactive microenvironmental cues can trigger proto-oncogenic genomic rearrangements and, subsequently, cancer. We also have evidence, acquired from immunohistochemistry studies of human samples, that prostate epithelium starts producing amyloid precursor protein before cancer occurs, during benign prostatic hyperplasia (BPH). The goal of this project is to determine whether reactive stroma-derived prolactin triggers the expression of the epithelial amyloid precursor protein, its processing enzyme BACE2, and downstream effectors implicated in oncogenesis. We hypothesize that prolactin expression in the stroma during BPH induces APP expression, leading to a genome rearrangement around the BACE2 locus in chromosome twenty-one that enables its transcription. We further propose that genomic rearrangement is a precursor of the TMPRSS-ERG translocation in chromosome twenty-one, commonly observed in prostate cancer. Our results show that in BPH, APP is secreted by both the epithelium and the stroma, independently of prolactin stimulation. Furthermore, we show that APP exposure increases BACE2 expression, potentially influencing a shift in chromatin structure/compartmentalization. These findings provide insight into APP-mediated biology within the hyperplastic prostate as a potential prelude to the TMPRSS-ERG translocation.
Recommended Citation
Then, Genesis, "Prolactin induction of Amyloid Deposition in the Prostate: A Mechanism for Progression from Benign Prostatic Hyperplasia to Prostate Cancer" (2026). CUNY Academic Works.
https://academicworks.cuny.edu/le_etds/49
