Effect of NUCKS-1 Overexpression on Cytokine Profiling in Obese Women with Breast Cancer


Background: Overweight and obesity are recognized as major drivers of cancers including breast cancer.Several cytokines, including interleukin-6 (IL-6), IL-10 and lipocalin 2 (LCN2), as well as dysregulated cellcycle proteins are implicated in breast carcinogenesis. The nuclear, casein kinase and cyclin-dependent kinasesubstrate-1 (NUCKS-1), is a nuclear DNA-binding protein that has been implicated in several human cancers,including breast cancer.
Objectives: The present study was conducted to evaluate NUCKS-1 mRNA expressionin breast tissue from obese patients with and without breast cancer and lean controls. NUCKS-1 expression wascorrelated to cytokine profiles as prognostic and monitoring tools for breast cancer, providing a molecular basisfor a causal link between obesity and risk. Materials and
Methods: This study included 39 females with breastcancer (G III) that was furtherly subdivided into two subgroups according to cancer grading (G IIIa and GIIIb) and 10 control obese females (G II) in addition to 10 age-matched healthy lean controls (G I). NUCKS-1expression was studied in breast tissue biopsies by means of real-time PCR (RT-PCR). Serum cytokine profileswere determined by immunoassay. Lipid profiles and glycemic status as well as anthropometric measures werealso recorded for all participants.
Results: IL-6, IL-12 and LCN2 were significantly higher in control obeseand breast cancer group than their relevant lean controls (p<0.05), while NUCKS-1 mRNA expression wassignificantly higher in the breast cancer group compared to the other groups (p<0.05). Significant higher levelsof IL-6, IL-12, and LCN2 as well as NUCKS-1 mRNA levels were reported in G IIIb than G IIIa, and positivelycorrelated with obesity markers in all obese patients.
Conclusions: Evaluation of cytokine levels as well as relatedgene expression may provide a new tool for understanding interactions for three axes of carcinogenesis, innateimmunity, inflammation and cell cycling, and hope for new strategies of management.