Integrins and Actions of Androgen in Breast Cancer

Abstract

Androgen has been shown to regulate male physiological activities and cancer proliferation. It is used to antagonize estrogen-induced proliferative effects in breast cancer cells. However, evidence indicates that androgen can stimulate cancer cell growth in estrogen receptor (ER)-positive and ER-negative breast cancer cells via different types of receptors and different mechanisms. Androgen-induced cancer growth and metastasis link with different types of integrins. Integrin αvβ3 is predominantly expressed and activated in cancer cells and rapidly dividing endothelial cells. Programmed death-ligand 1 (PD-L1) also plays a vital role in cancer growth. The part of integrins in action with androgen in cancer cells is not fully mechanically understood. To clarify the interactions between androgen and integrin αvβ3, we carried out molecular modeling to explain the potential interactions of androgen with integrin αvβ3. The androgen-regulated mechanisms on PD-L1 and its effects were also addressed.

Polycystic ovary syndrome and risk of breast cancer in premenopausal and postmenopausal women: a nationwide population-based cohort study

“…Additionally, PCOS is associated with later age at menopause, resulting in a longer lifetime exposure to estrogens [36]. As for the role of PCOS-related hyperandrogenism in breast cancer, evidence indicates that androgens play a role in cancer progression through activation of integrins, although these mechanisms are not fully understood [37]. Lastly, a high proportion of women with a history of PCOS are also previous users of combined hormonal contraceptives, perhaps at an early age and for a prolonged period.…”