Abstract LB-204: Oncogenic Ras signaling requires serine protease hepsin to induce invasive breast cancer phenotype

Author(s):  
Shishir Mani Pant ◽  
Topi Tervonen ◽  
Denis Belitskin ◽  
Johanna Englund ◽  
Emmy Verschuren ◽  
...  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Patrick D. Rädler ◽  
Barbara L. Wehde ◽  
Aleata A. Triplett ◽  
Hridaya Shrestha ◽  
Jonathan H. Shepherd ◽  
...  

AbstractClaudin-low breast cancer represents an aggressive molecular subtype that is comprised of mostly triple-negative mammary tumor cells that possess stem cell-like and mesenchymal features. Little is known about the cellular origin and oncogenic drivers that promote claudin-low breast cancer. In this study, we show that persistent oncogenic RAS signaling causes highly metastatic triple-negative mammary tumors in mice. More importantly, the activation of endogenous mutant KRAS and expression of exogenous KRAS specifically in luminal epithelial cells in a continuous and differentiation stage-independent manner induces preneoplastic lesions that evolve into basal-like and claudin-low mammary cancers. Further investigations demonstrate that the continuous signaling of oncogenic RAS, as well as regulators of EMT, play a crucial role in the cellular plasticity and maintenance of the mesenchymal and stem cell characteristics of claudin-low mammary cancer cells.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22188-e22188
Author(s):  
A. Khan ◽  
Y. E. Tovar ◽  
C. Rodriguez ◽  
A. L. Huerta ◽  
B. Rajabi ◽  
...  

e22188 Background: In daily oncology practice, triple-negative invasive breast cancer is defined by negative immunohistochemistry for ER, PR and HER-2. Patients with this phenotype experience poor prognosis due to limited treatment options and intrinsic tumor biology. In a population-based case-control study, the Carolina Breast Cancer Study (Carey et al, JCO, 2004: suppl; abstr 9510), the triple-negative phenotype in African-American women represented 33.9% of the tumors. We aimed to identify the incidence of triple-negative invasive breast cancer in a group of women living in a predominantly Hispanic population on the Texas- Mexico border. Methods: We collected retrospective data for all invasive breast cases diagnosed between January 2005 and December 2008 at our affiliated county hospital. Clinical and pathological features were summarized. ER, PR and HER-2 was performed by immunohistochemistry. Results: 309 patients with invasive breast cancer were identified. 23.9% (74 patients) of all breast cancer patients were triple-negative. 70 of the 74 subjects (94.6%) were Hispanic. There was equal distribution of patients over and under the age of 50. Histologically all cases were invasive ductal carcinoma. The vast majority had grade 3 tumors (82%) with a high Ki-67 proliferative index (97%). Lymphovascular invasion was present in 38 patients (51.4%). Distant metastases at diagnosis was found in 4 patients (5.4%). Conclusions: In our population-based study the proportion of triple-negative invasive breast cancer phenotype was not as high as in the Carolina Breast Cancer Study, but does reflect that a quarter of the patients with invasive breast cancer in this growing Hispanic population may carry this phenotype. The triple-negative phenotype was strongly associated with high tumor grade and proliferative index. No significant financial relationships to disclose.


Marine Drugs ◽  
2017 ◽  
Vol 15 (9) ◽  
pp. 290 ◽  
Author(s):  
Fatma Al-Awadhi ◽  
Lilibeth Salvador ◽  
Brian Law ◽  
Valerie Paul ◽  
Hendrik Luesch

2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Mohammadreza Zamanian ◽  
Lama Abdel Qader Hamadneh ◽  
Abhi Veerakumarasivam ◽  
Sabariah Abdul Rahman ◽  
Shamarina Shohaimi ◽  
...  

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