Discipline: Biological Sciences
Subcategory: Cancer Research
Bosson-Sora M. Ahouti - University of the District of Columbia
Co-Author(s): Thomas Elimihele and Brandy Huderson
Breast cancer is a leading cause of cancer death among women and a major public health problem. Breast cancers are initially asses based on the presence or absence of the estrogen receptor (ER). Interestingly, the androgen receptor (AR), a member of the super family of ligand-activated steroid hormone receptors, has been shown to be present in 60-80 % of breast cancer. AR has been shown to inhibit tumor growth in the presence of ER; however in ER-negative (ER-) breast cancer cells, AR acts a driver of proliferation. Previously published data has shown a role dysregulated Wnt expression in aggressive tumors and furthermore, that AR is able to signal through Wnt pathway to promote tumor cell malignancy in a ligand-independent manner. Exosomes are extracellular vesicles that are released from cells and used to remove and transport macro molecules. Exosomes have previously been shown to deliver macromolecules such as proteins and miRNA to recipient cells. The purpose of this study was to evaluate the ability of exosomes derived from cells with differing hormone receptor expression classifications to affect cellular processes. We hypothesized that exosomes derived from estrogen receptor-negative (ER-)/androgen receptor-positive (AR+) breast cancer cells can effect Wnt 7b expression by modulating AR signaling in AR+ recipient cells. Prostate cancer cells, C42B, were incubated with previously collected exosomes from estrogen receptor-negative (ER-)/AR+ MDA MB 231, MDA MB 453, or ER+/AR- MCF-7 breast cancer cell lines. Effects of cancer cell-derived exosomes on AR signaling were evaluated by measuring expression of known AR target, Wnt 7b using qRT-PCR. Incubation of C42B cells with exosomes ER-/AR+ MDA MB 453 resulted in decreased expression of Wnt 7b, while incubation with MDA MB 231 and MCF-7 cells increased Wnt 7b expression. Interestingly, expression of Wnt 7b by C42b cells incubated with MCF-7 was similar to expression levels for C42b cells treated with AR antagonist flutamide. In conclusion, the ability of cancer-derived exosomes to modulation cellular processes is dependent on the donor cell. Further, this data combined with previous data from our lab suggest that these altered gene expression patterns are in fact reminiscent of donor cells expression patterns.Ahouti ABRCMS 2017.docx
Funder Acknowledgement(s): Funding was provided by the NSF/HRD1531014 and 1622811 grants awarded to the UDC STEM Center.
Faculty Advisor: Brandy Huderson, firstname.lastname@example.org
Role: All research presented was conducted by me.