Hormones and their receptors play an important role in the development and progression of
breast cancer.
Hormones regulate the proliferation of
breast cancer cells through binding between
estrogen or
progestins and
steroid receptors that may reside in the cytoplasm or be transcriptionally activated as
steroid-
protein nuclear receptor complexes. However, receptors for nonpeptide
hormones also exist in the plasma membrane. Via those receptors,
hormones are able to stimulate
breast cancer cell proliferation when activated.
Integrins are heterodimeric structural
proteins of the plasma membrane. Their primary functions are to interact with
extracellular matrix proteins and
growth factors. Recently,
integrin αvβ3 has been identified as a receptor for nonpeptide
hormones, such as
thyroid hormone and
dihydrotestosterone (DHT). DHT promotes the proliferation of human
breast cancer cells through binding to
integrin αvβ3. A receptor for
resveratrol, a
polyphenol stilbene, also exists on this
integrin in
breast cancer cells, mediating the anti-proliferative, pro-apoptotic action of the compound in these cells. Unrelated activities of DHT and
resveratrol that originate at
integrin depend upon downstream stimulation of
mitogen-activated protein kinase (MAPK, ERK1/2) activity, suggesting the existence of distinct, function-specific pools of ERK1/2 within the cell. This review will discuss the features of these receptors in
breast cancer cells, in turn suggesting clinical applications that are based on the interactions of
resveratrol/DHT with
integrin αvβ3 and other
androgen receptors.