Radio resistance in breast cancer cells is mediated through TGF-β signalling, hybrid epithelial-mesenchymal phenotype and cancer stem cells

Publication date: March 2019Source: Biomedicine & Pharmacotherapy, Volume 111Author(s): Poonam Yadav, Bhavani S. ShankarAbstractAimsA major obstacle for effective cancer treatment by radiation therapy is the development of radio-resistance and identification of underlying mechanisms and activated pathways will lead to better combination therapies.Main methodsIrradiated MCF-7 and MDA-MB-231 breast cancer cell lines were characterised following different recovery periods. Proliferation was assessed by MTT, BrdU and clonogenic assays and apoptosis by Annexin V/ propidium iodide staining and flow cytometry. Gene expression was monitored by real time PCR/ELISA/antibody labelling and migration using transwell inserts.Key findingsBreast cancer cell lines exposed to 6 Gy followed by recovery period for 7 days (D7-6 G) had increased ability for proliferation as well as apoptosis. D7-6 G from both cell lines had increased expression of transforming growth factor isoforms (TGF)-β1, β2 and β3, their receptors TGF-βR1 and TGF-βR2 which are known for such dual effects. The expression of downstream transcription factors Snail, Zeb-1 and HMGA2 also showed a differential pattern in D7-6 G cells with upregulation of at least two of these transcription factors. D7-6 G cells from both cell lines displayed hybrid epithelial-mesenchymal (E/M) phenotype with increased expression of E/M markers and migration. D7-6 G cells had increased expression of cancer stem cells markers Oct4, S...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research