Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation
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Sachin K. Deshmukh1,*, Sanjeev K. Srivastava1,*, Arun Bhardwaj1, Ajay P. Singh1,2, Nikhil Tyagi1, Saravanakumar Marimuthu1, Donna L. Dyess1, Valeria Dal Zotto3, James E. Carter3 and Seema Singh1
1 Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA
2 Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, Alabama, USA
3 Department of Pathology, College of Medicine, University of South Alabama, Mobile, Alabama, USA
* These authors contributed equally in this manuscript
Seema Singh, email:
Keywords: racial disparity, breast cancer, resistin, IL-6, STAT3, inflammatory cytokine
Received: January 28, 2015 Accepted: February 19, 2015 Published: March 14, 2015
African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity.
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