Estrogen and the estrogen receptors (ERs) are key regulators in the progression of breast cancer. For this reason, selective estrogen receptor modulators, like Tamoxifen, were developed and have been used for decades to suppress the estrogen signaling pathway in women with breast cancer. Nevertheless, many tumors develop resistance to estrogen receptor modulator therapies. Thus, new molecular targets in the management of ER-positive breast cancer are required.
Nuclear receptor coactivator NCOA3 was previously identified as a relevant player in breast cancer biology. NCOA3 is amplified and overexpressed in a significant portion of breast tumors and, in ER-positive breast cancers, is required for maximal activity of ERs. In patients with ER-positive tumors treated with the selective ER-modulator Tamoxifen, high levels of NCOA3 are associated with resistance to therapy and a shorter disease free survival. Based on these observations, NCOA3 has been under investigation as a target for treatment of breast cancer.
PLAC1 was first described by the Türeci and Sahin lab as a promising candidate for targeted therapies of breast cancer, including ER-positive tumors (http://cancerres.aacrjournals.org/content/67/19/9528.abstract; http://www.jbc.org/content/284/42/28607.full).
Now, in the paper of Wagner et al., a link between PLAC1 and NCOA3 has been established. In the publication, Wagner et al. show that NCOA3 is necessary for increased expression of PLAC1 in an ER-dependent manner. Moreover, a relevant correlation of PLAC1 expression and NCOA3 overexpression in human breast cancer tissues restricted to ER-positive samples was shown. These data suggest a role of PLAC1 in the NCOA3/ER-signaling pathway and might open new therapeutic concepts for breast cancer.
Breast cancer is the most common cancer among women, with an estimated 1,000,000 new cases worldwide each year, (60,000 new cases in Germany). Although there has been a steady decrease in breast cancer mortality since the early 90s largely due to improvements in the early detection and treatment of breast tumors, 20 percent of all breast cancer patients will still die.
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Immunohistochemistry of breast cancer tissue using a PLAC1-specific antibody