title: 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.
abstract: 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.
authors: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA.
authors: Sachin K
authors: SK
authors: Deshmukh
authors: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA.
authors: Sanjeev K
authors: SK
authors: Srivastava
authors: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA.
authors: Arun
authors: A
authors: Bhardwaj
authors: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA.|Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, Alabama, USA.
authors: Ajay P
authors: AP
authors: Singh
authors: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA.
authors: Nikhil
authors: N
authors: Tyagi
authors: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA.
authors: Saravanakumar
authors: S
authors: Marimuthu
authors: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA.
authors: Donna L
authors: DL
authors: Dyess
authors: Department of Pathology, College of Medicine, University of South Alabama, Mobile, Alabama, USA.
authors: Valeria
authors: V
authors: Dal Zotto
authors: Department of Pathology, College of Medicine, University of South Alabama, Mobile, Alabama, USA.
authors: James E
authors: JE
authors: Carter
authors: Department of Oncologic Sciences, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA.
authors: Seema
authors: S
authors: Singh
mesh_terms: D001741:Black or African American / Q000235:genetics; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D054624:Health Status Disparities; D006801:Humans; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010766:Phosphorylation; D034622:RNA Interference; D052243:Resistin / Q000097:blood* / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D059016:Tumor Microenvironment; D044465:White People / Q000235:genetics; D000093242:Interleukin-6 Inhibitors
chemical_list: D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015850:Interleukin-6; D052243:Resistin; D050796:STAT3 Transcription Factor; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; C499624:RETN protein, human; C494086:STAT3 protein, human
keywords: IL-6; STAT3; breast cancer; inflammatory cytokine; racial disparity; resistin