DEAR1 Is a Dominant Regulator of Acinar Morphogenesis and an Independent Predictor of Local Recurrence-Free Survival in Early-Onset Breast Cancer

Abstract

Ann Killary and colleagues describe a new gene that is genetically altered in breast tumors, and that may provide a new breast cancer prognostic marker.

TRIM Protein-Mediated Regulation of Inflammatory and Innate Immune Signaling and Its Association with Antiretroviral Activity

“…In addition to playing a role in innate immune signaling as documented here, missense mutations and homozygous deletion that abrogate TRIM62 expression have been associated with early onset of breast cancer (58). TRIM62, also known as DEAR1, is required for proper acinar morphogenesis in the mammary gland.…”

“…TRIM62, also known as DEAR1, is required for proper acinar morphogenesis in the mammary gland. Three-dimensional (3D) culture of breast epithelial cells with TRIM62 expression silenced did not form a bona fide lumen due to a failure in apoptosis exemplified by reduced caspase 3 activation (58). Interestingly, TLR activation and subsequent TRIF signaling can result in the induction of apoptosis (59,60).…”

The need for complex 3D culture models to unravel novel pathways and identify accurate biomarkers in breast cancer

“…In fact, the multi-acinar phenotype induced by HER2 in MCF10A cells propagated in 3D lrECM shows great similarities with human HER2 amplified DCIS lesions [111]. Also DEAR1 , a gene encoding a member of the TRIM subfamily of RING finger proteins, has been reported to be a dominant regulator of acinar morphogenesis in normal mammary gland cells and to be mutated/ deleted in breast cancer [115]. The MCF10A model has also been used to unravel signaling pathways in breast cells.…”

Methyl Sulfone Manifests Anticancer Activity in a Metastatic Murine Breast Cancer Cell Line and in Human Breast Cancer Tissue - Part 2: Human Breast Cancer Tissue

“…Furthermore, the higher the degree of disorder within malignant breast tissue, the worse the prognosis [24,25,26]. Conversely, a protein that plays a role in maintaining tissue architecture, DEAR1, is also a tumor suppressor protein [27]. …”