Marginal zinc intake impairs mammary gland involution, increases oxidative stress and disrupts ductal integrity abrogating the protective effect of lactation on breast tumorigenesis in a mouse model
Breast cancer; Collagen; Ductal hyperplasia; Estrogen receptor;
Abstract:
Breast cancer is the most common cancer among women. While breastfeeding can reduce breast cancer risk, several studies found no protective effect. We showed that marginal zinc (Zn) intake compromises mammary gland (MG) expansion and function during lactation and is associated with hallmarks of pre-neoplastic lesions such as collagen deposition, macrophage infiltration, and ductal hyperplasia in the MG of nulliparous mice. Herein, we hypothesized that marginal Zn deficiency abrogates the protective effect of breastfeeding on breast cancer risk. C57BL/6 mice were fed a Zn adequate (ZA; 30mg Zn/kg) or Zn deficient (ZD; 15mg Zn/ kg) diet. Mice were bred, and 2 wk post-weaning were gavaged with 7,12-dimethylbenzanthracene (DMBA; 1mg/0.1mL corn oil) or corn oil (control) weekly for 4 wk. Tumor progression was monitored for 24 wk. ZD mice had lower matrix metalloproteinase 2 activity (p<0.01) and insufficient involution, shorter tumor latency (p=0.05), and tended to have greater palpable (35% vs 12% p=0.137) and non-palpable tumors (p=0.08). ZD mice had greater oxidative stress, e-cadherin expression and collagen deposition in the MG. Moreover, mammary tumors in ZD mice accumulated Zn and had characteristics of a more invasive phenotype. Our results suggest that consuming inadequate dietary Zn may impair post- lactational regression and abrogate the protective effect of breastfeeding on breast cancer.
