Acute and Chronic Exposure of Nickel Promotes Breast Cancer Cell Growth

Abstract

Increasing incidences of breast cancer have been a global public health concern, however the underlying cause remains unknown. Studies have suggested that exposure to elevated levels of heavy metals has been associated with deregulated cell growth and cell death. Heavy metals including nickel (Ni2+) are known to mimic the effects of estrogen and promote breast cancer cell growth, but its mechanism of action is unclear. To understand Ni2+ carcinogenicity, we examined the effects of Ni2+ on ER+ breast cancer cell (MCF‐7) growth. Our results suggest that acute and chronic Ni2+ exposure increases MCF‐7 cell growth. Further analysis at the molecular level indicate that the expression of several cell cycle genes were upregulated, whereas the expression of two cyclin‐dependent kinase inhibitors (CKI), p21 and p27 were significantly decreased in response to Ni2+ exposure. The ability of CKIs to induce cell cycle arrest is dependent upon their interaction with their respective cyclin/cyclin dependent kinase complex. Understanding the molecular mechanism of how nickel regulates the expression of CKIs, and the role of ERα in this process will provide insights to how Ni2+ contributes to breast cancer etiology.