Abstract
African Americans (AA) have higher death rates due to prostate and breast cancer as compared to Caucasian Americans (CA), and few biomarkers have been associated with this disparity. In our study we investigated whether epithelial-mesenchymal transition (EMT) with a focus on Snail and Cathepsin L (Cat L), could potentially be two markers associated with prostate and breast health disparities. We have previously shown that Snail can increase Cat L protein and activity in prostate and breast cancer. Western blot and real-time PCR analyses showed that mesenchymal protein expression (Snail, vimentin, Cat L) and Cat L activity (shown by zymography) was higher in AA prostate cancer cells as compared to CA normal transformed RWPE-1 prostate epithelial cells, and androgen-dependent cells, and comparable to metastatic CA cell lines. With respect to breast cancer, mesenchymal markers were higher in TNBC compared to non-TNBC cells. The higher mesenchymal marker expression was functionally associated with higher proliferative and migratory rates. Immunohistochemistry showed that both nuclear Snail and Cat L expression was significantly higher in cancer compared to normal for CA and Bahamas prostate patient tissue. Interestingly, AA normal tissue stained higher for nuclear Snail and Cat L that was not significantly different to cancer tissue for both prostate and breast tissue, but was significantly higher than CA normal tissue. AA TNBC tissue also displayed significantly higher nuclear Snail expression compared to CA TNBC, while no significant differences were observed with Luminal A cancer tissue. Therefore, increased EMT in AA compared to CA that may contribute to the more aggressive disease.
Highlights
Prostate cancer is the most common non-cutaneous cancer in men and is considered the second most frequent cause of death in men in the United States [1]
We examined the expression of Epithelial Mesenchymal Transition (EMT) markers in a panel of prostate cancer cells lines of increasing aggressiveness, and of Caucasian American men (CA) and American men (AA) origin, by western blot analysis, as well as Cathepsin L (Cat L) activity by zymography
African American men (AA) have the higher incidence and mortality rate due to prostate cancer compared to Caucasian American men (CA) [2]
Summary
Prostate cancer is the most common non-cutaneous cancer in men and is considered the second most frequent cause of death in men in the United States [1]. African American men (AA) have a higher incidence rate and two-fold increased mortality due to prostate cancer as compared to Caucasian American men (CA) [2]. The mortality due to TNBC is higher in African-American and Latino patients, compared to other ethnic groups [5]. The primary cause of breast cancer death is metastasis, which is regulated by several factors and signaling pathways such as EMT, a dynamic process that promotes cell motility with decreased adhesive ability between cells to their neighbors [7]
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