E-TABM-718 - Transcription profiling of rat DMBA induced mammary adeno carcinoma
Submitted on 19 June 2009, released on 22 June 2009, last updated on 2 May 2014
Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT). We report that hyperbaric oxygen (HBO) treatment induced mesenchymal-to-epithelial transition (MET) in a dimetyl-α-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO2 = 2 bar, 4 exposures à 90 minutes), whereas the control group was housed under normal atmosphere (1 bar, pO2 = 0.2 bar). Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (~16%) after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100 % in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the “switches” of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects.
transcription profiling by array, co-expression, treatment
Hyperoxic treatment induces mesenchymal-to-epithelial transition in a rat adenocarcinoma model. Moen I, Øyan AM, Kalland KH, Tronstad KJ, Akslen LA, Chekenya M, Sakariassen PØ, Reed RK, Stuhr LE. :e6381 (2009), PMID:19636430
Hyperoxic Treatment induces Mesenchymalto-Epithelial Transition in a Rat Adenocarcinoma Model. Ingrid Moen1, Anne Margrete Øyan2,3, Karl Henning Kalland2,3, Karl Johan Tronstad1, Lars Andreas Akslen2,4, Martha Chekenya1, Per Øystein Sakariassen1, Rolf Kåre Reed1, Linda Elin Birkhaug Stuhr1. PLoS One (2009)