Leptin in Breast Cancer: Its Relationship with Insulin, Estrogens and Oxidative Stress

Breast cancer is the most common cancer in women. Several risk factors such as age, family history of breast cancer, marital status, early menarche and late menopause are related to breast cancer. Obesity is also a main health problem associated with breast cancer incidence and subsequent mortality. Association between obesity and expansion of breast cancer may be due to excessive sex steroid hormone production, particularly estrogen. Moreover, adipose tissue is not only a source of estrogen secretion, but also a producer of certain ‘‘adipocytokines” including leptin. Leptin is a neuroendocrine hormone with 167 amino acid produced predominantly by white adipose tissue. Leptin after binding to receptor activate JAK/STAT/MAP. Leptin also increased expression of cyclin D1 and cdk2 and induces proliferation. It may also develop mammary tumor growth via multiple mechanisms like pro-inflammatory, oxidative, and anti-apoptotic proangiogenic effects. Leptin can increase aromatase activity in MCF-7 cell line which may increase estrogen production and subsequently induce tumor cell growth. Hyperinsulinism through enhanced leptin production by adipose tissue can affect poor breast cancer prognosis.