PLC‐β2 is modulated by low oxygen availability in breast tumor cells and plays a phenotype dependent role in their hypoxia‐related malignant potential. Issue 12 (19th January 2016)

• Record Type: Journal Article
• Authors: Brugnoli, Federica; Grassilli, Silvia; Al‐Qassab, Yasamin; Capitani, Silvano; Bertagnolo, Valeria
• Is Part Of: Molecular carcinogenesis. Volume 55:Issue 12(2016:Dec.)
• Page Start: 2210
• Page End: 2221
• Publication Date: 2016-01-19
• Subjects: breast cancer -- hypoxia -- PLC‐β2 -- EMT -- CD133; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22462
• Languages: English
• ISSNs: 0899-1987

Abstract

Abstract : Limited oxygen availability plays a critical role in the malignant progression of breast cancer by orchestrating a complex modulation of the gene transcription largely dependent on the tumor phenotype. Invasive breast tumors belonging to different molecular subtypes are characterized by over‐expression of PLC‐β2, whose amount positively correlates with the malignant evolution of breast neoplasia and supports the invasive potential of breast tumor cells. Here we report that hypoxia modulates the expression of PLC‐β2 in breast tumor cells in a phenotype‐related manner, since a decrease of the protein was observed in the BT‐474 and MCF7 cell lines while an increase was revealed in MDA‐MB‐231 cells as a consequence of low oxygen availability. Under hypoxia, the down‐modulation of PLC‐β2 was mainly correlated with the decrease of the EMT marker E‐cadherin in the BT‐474 cells and with the up‐regulation of the stem cell marker CD133 in MCF7 cells. The increase of PLC‐β2 induced by low oxygen in MDA‐MB‐231 cells supports the hypoxia‐related reorganization of actin cytoskeleton and sustains invasion capability. In all examined cell lines, but with an opposite role in the ER‐positive and ER‐negative cells, PLC‐β2 was involved in the hypoxia‐induced increase of HIF‐1α, known to affect both EMT and CD133 expression. Our data include PLC‐β2 in the complex and interconnected signaling pathways induced by low oxygen availability in breast tumor cells and suggest that the forced modulation of PLC‐β2 programmed on the basis of tumor phenotype may prevent the malignant progression of breast neoplasia as a consequence of intra‐tumoral hypoxia. © 2016 Wiley Periodicals, Inc.