Zymogen granule protein 16B (ZG16B) is a druggable epigenetic target to modulate the mammary extracellular matrix.

High tissue density of the mammary gland is considered a pro-tumorigenic factor, hence suppressing the stimuli that induce matrix buildup carries the potential for cancer interception. We found that in non-malignant mammary epithelial cells the combination of the chemopreventive agents bexarotene (Bex) and carvedilol (Carv) suppresses the zymogen granule protein 16B (ZG16B, PAUF) through an interaction of ARID1A with a proximal enhancer. Bex + Carv also reduced ZG16B levels in vivo in normal breast tissue and MDA-MB231 tumor xenografts.

Redistribution of the SWI/SNF Complex Dictates Coordinated Transcriptional Control over Epithelial-Mesenchymal Transition of Normal Breast Cells through TGF-β Signaling.

Therapeutic targets in cancer cells defective for the tumor suppressor ARID1A are fundamentals of synthetic lethal strategies. However, whether modulating ARID1A function in premalignant breast epithelial cells could be exploited to reduce carcinogenic potential remains to be elucidated. In search of chromatin-modulating mechanisms activated by anti-proliferative agents in normal breast epithelial (HME-hTert) cells, we identified a distinct pattern of genome-wide H3K27 histone acetylation marks characteristic for the combined treatment by the cancer preventive rexinoid bexarotene (Bex) and carvedilol (Carv).

The Role of ARID1A in the Nonestrogenic Modulation of IGF-1 Signaling.

Unlabelled: Gaining pharmacologic access to the potential of ARID1A, a tumor suppressor protein, to mediate transcriptional control over cancer gene expression is an unresolved challenge. Retinoid X receptor ligands are pleiotropic, incompletely understood tools that regulate breast epithelial cell proliferation and differentiation. We found that low-dose bexarotene (Bex) combined with the nonselective beta-blocker carvedilol (Carv) reduces proliferation of MCF10DCIS.