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HB-EGF Is Associated With DNA Damage and Mcl-1 Turnover in Human Glioma Cell Lines Treated by Temozolomide

HB-EGF Is Associated With DNA Damage and Mcl-1 Turnover in Human Glioma Cell Lines Treated by Temozolomide

Quentin Séry, Marion Rabé, Lisa Oliver, François M Vallette, Catherine Gratas

Biochem Biophys Res Commun. 2017 Dec 2;493(4):1377-1383.

PMID: 28970067

Abstract:

Temozolomide (TMZ) is the main chemotherapeutic agent used for treating newly diagnosed Glioblastoma Multiforme (GBM), the most frequent malignant brain tumors in adults. This alkylating agent induces DNA double strand breaks (DSBs) which in turn lead to apoptosis by activating the Bcl-2 controlled mitochondrial pathway. However, GBM invariably recur as tumors become resistant to TMZ. We investigated the implication of EGFR ligands in this resistance and we found that the pro Heparin Binding Epidermal Growth Factor (proHB-EGF) expression is linked to the early response to TMZ in human glioma cell lines. However, HB-EGF does not affect apoptosis per se although its expression is associated with the degradation of Mcl-1. HB-EGF is implicated in DSBs repair as silencing of HB-EGF increased γH2AX foci half-life as well as USP9X expression, two features that could be linked to the observed effect on Mcl-1. Our data demonstrate a new role for HB-EGF in TMZ treated cell lines.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413234	HB-EGF human			Price

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