Aberrant activation of NF-κB signaling in mammary epithelium leads to abnormal growth and ductal carcinoma in situ

摘要: Approximately 1 in 5 women diagnosed with breast cancer are considered to have situ disease, most often termed ductal carcinoma (DCIS). Though recognized as a risk factor for the development of more invasive cancer, it remains unclear what factors contribute DCIS development. It has been shown that inflammation contributes progression variety tumor types, and nuclear kappa B (NF-κB) is master-regulator inflammatory signaling. However, contributions NF-κB signaling initiation less well understood. Aberrant up-regulation activity, either systemically or locally within breast, could occur due commonly experienced stimuli such acute infection, obesity, psychological stress. In this study, we seek determine if activation mammary epithelium play role formation hyperplastic lesions. Our studies utilize doxycycline-inducible transgenic mouse model which constitutively active IKKβ expressed specifically epithelium. All previously published models modulation virgin gland constitutive models, transgene knock-out present throughout life animal. For first time, will induce at later time points after normal ducts formed, thus being able can promote pre-malignant changes We found even short pulse profound remodeling structures. Short-term created hyperproliferative, enlarged filled lumens. Increased expression markers was concurrent down-regulation hormone receptors epithelial differentiation. Furthermore, oncoprotein mucin 1, known be up-regulated human DCIS, over-expressed mislocalized activated tissue. These results indicate aberrant lead molecular morphological consistent earliest stages cancer. Thus, inhibition following initial signs growth represent an important opportunity prevention.