Abstract
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 cell cycle proteins are implicated in breast carcinogenesis. The nuclear, casein kinase and cyclin-dependent kinase substrate-1 (NUCKS-1), is a nuclear DNA-binding protein that has been implicated in several human cancers, including breast cancer. The present study was conducted to evaluate NUCKS-1 mRNA expression in breast tissue from obese patients with and without breast cancer and lean controls. NUCKS-1 expression was correlated to cytokine profiles as prognostic and monitoring tools for breast cancer, providing a molecular basis for a causal link between obesity and risk. This study included 39 females with breast cancer (G III) that was furtherly subdivided into two subgroups according to cancer grading (G IIIa and G IIIb) and 10 control obese females (G II) in addition to 10 age-matched healthy lean controls (G I). NUCKS-1 expression was studied in breast tissue biopsies by means of real-time PCR (RT-PCR). Serum cytokine profiles were determined by immunoassay. Lipid profiles and glycemic status as well as anthropometric measures were also recorded for all participants. IL-6, IL-12 and LCN2 were significantly higher in control obese and breast cancer group than their relevant lean controls (p<0.05), while NUCKS-1 mRNA expression was significantly higher in the breast cancer group compared to the other groups (p<0.05). Significant higher levels of IL-6, IL-12, and LCN2 as well as NUCKS-1 mRNA levels were reported in G IIIb than G IIIa, and positively correlated with obesity markers in all obese patients. Evaluation of cytokine levels as well as related gene expression may provide a new tool for understanding interactions for three axes of carcinogenesis, innate immunity, inflammation and cell cycling, and hope for new strategies of management.
Highlights
Obesity is a growing health problem increasing worldwide, excess body weight has been linked to an increased risk of postmenopausal breast cancer, and growing evidence suggests that obesity is associated with poor prognosis in women diagnosed with earlystage breast cancer (Ligibel, 2011)
IL-6, IL-12 and lipocalin 2 (LCN2) were significantly higher in control obese and breast cancer group than their relevant lean controls (p
In this current study high values of body mass index (BMI), waist circumference (WC), FBG, fasting blood insulin as well as HOMA-IR index were detected in obese patients than control ones
Summary
Obesity is a growing health problem increasing worldwide, excess body weight has been linked to an increased risk of postmenopausal breast cancer, and growing evidence suggests that obesity is associated with poor prognosis in women diagnosed with earlystage breast cancer (Ligibel, 2011). The role of lipids in cancer in maintenance of cell integrity is well documented, any alteration in the plasma lipid profile in breast cancer cases can increase its risk status and its measurement may be helpful in evaluation of prognostic and diagnostic importance of the disease (Cejas et al, 2004). Several cytokines, including interleukin-6 (IL-6), IL-10 and lipocalin 2 (LCN2), as well as dysregulated cell cycle proteins are implicated in breast carcinogenesis. Objectives: The present study was conducted to evaluate NUCKS-1 mRNA expression in breast tissue from obese patients with and without breast cancer and lean controls. NUCKS-1 expression was correlated to cytokine profiles as prognostic and monitoring tools for breast cancer, providing a molecular basis for a causal link between obesity and risk. Conclusions: Evaluation of cytokine levels as well as related gene expression may provide a new tool for understanding interactions for three axes of carcinogenesis, innate immunity, inflammation and cell cycling, and hope for new strategies of management
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