Breast cancer is a highly heterogeneous disease, encompassing many subtypes that have distinct origins, behaviors, and prognoses. Although traditionally seen as a
genetic disease,
breast cancer is now also known to involve epigenetic abnormalities. Epigenetic regulators, such as
DNA methyltransferases and
histone-modifying
enzymes, play essential roles in gene regulation and
cancer development. Dysregulation of epigenetic regulator activity has been causally linked with
breast cancer pathogenesis. Hairless (HR) encodes a 130-kDa
transcription factor that is essential for development and tissue homeostasis. Its role in transcription regulation is partly mediated by its interaction with multiple
nuclear receptors, including
thyroid hormone receptor,
retinoic acid receptor-related orphan receptors, and
vitamin D receptor. HR has been studied primarily in epidermal development and homeostasis. Hr-mutant mice are highly susceptible to ultraviolet- or
carcinogen-induced skin
tumors. Besides its putative
tumor suppressor function in skin, loss of HR function has also been implicated in increased
leukemia susceptibility and promotes the growth of
melanoma and
brain cancer cells. HR has also been demonstrated to function as a
histone H3 lysine 9 demethylase. Recent genomics studies have identified HR mutations in a variety of human
cancers, including
breast cancer. The anticancer function and mechanism of action by HR in mammary tissue remains to be investigated. Here, we review the emerging role of HR, its
histone demethylase activity and
histone methylation in
breast cancer development, and potential for epigenetic
therapy.