Association of Epithelial Mesenchymal Transition with prostate and breast health disparities

被引:8
|
作者
Burton, Liza J. [1 ]
Hawsawi, Ohuod [1 ]
Loyd, Quentin [1 ]
Henderson, Veronica [1 ]
Howard, Simone [1 ]
Harlemon, Maxine [1 ,2 ]
Ragin, Camille [2 ,3 ]
Roberts, Robin [2 ,4 ]
Bowen, Nathan [1 ]
Gacii, Andrew [2 ,5 ]
Odero-Marah, Valerie [1 ,2 ]
机构
[1] Clark Atlanta Univ, Dept Biol Sci, Ctr Canc Res & Therapeut Dev, Atlanta, GA 30314 USA
[2] African Caribbean Canc Consortium, Philadelphia, PA USA
[3] Temple Hlth, Fox Chase Canc Ctr, Philadelphia, PA USA
[4] Univ West Indies, Sch Clin Med & Res, Nassau, Bahamas
[5] Kenyatta Natl Hosp, Dept Lab Med, Nairobi, Kenya
来源
PLOS ONE | 2018年 / 13卷 / 09期
基金
美国国家卫生研究院;
关键词
NUCLEAR CATHEPSIN-L; CANCER-CELLS; E-CADHERIN; CYSTEINE CATHEPSINS; SIGNALING PATHWAY; AFRICAN-AMERICAN; EXPRESSION; SNAIL; LOCALIZATION; KAISO;
D O I
10.1371/journal.pone.0203855
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:16
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