Sensitivity to cisplatin in primary cell lines derived from human glioma correlates with levels of EGR-1 expression

Antonella Calogero,Antonio Porcellini,Donatella Ponti,Cinzia Fabbiano,Antonietta Arcella,Vincenza Lombari,Giuseppe Ragona,Massimo Miscusi

doi:10.1186/1475-2867-11-5

Abstract

BackgroundLess than 30% of malignant gliomas respond to adjuvant chemotherapy. Here, we have asked whether variations in the constitutive expression of early-growth response factor 1 (EGR-1) predicted acute cytotoxicity and clonogenic cell death in vitro, induced by six different chemotherapics.Materials and methodsCytotoxicity assays were performed on cells derived from fresh tumor explants of 18 human cases of malignant glioma. In addition to EGR-1, tumor cultures were investigated for genetic alterations and the expression of cancer regulating factors, related to the p53 pathway.ResultsWe found that sensitivity to cisplatin correlates significantly with levels of EGR-1 expression in tumors with wild-type p53/INK4a/p16 status.ConclusionIncreased knowledge of the mechanisms regulating EGR-1 expression in wild-type p53/INK4a/p16 cases of glioma may help in the design of new chemotherapeutic strategies for these tumors.

Highlights

Malignant brain tumors of glial origin are highly invasive and poorly sensitive to anti-proliferative drugs, with only 20-30% of patients responding to chemotherapy
We found that sensitivity to cisplatin correlates significantly with levels of early-growth response factor 1 (EGR-1) expression in tumors with wild-type p53/INK4a/p16 status
We have examined the response of freshly derived primary cell lines of malignant glioma, each established in our laboratory from a different donor, to cisplatin and five other cytotoxic drugs of relevant use

Summary

Introduction

Malignant brain tumors of glial origin are highly invasive and poorly sensitive to anti-proliferative drugs, with only 20-30% of patients responding to chemotherapy. Either positively or negatively, target genes such as TGF-b, cyclin D1, c-jun, PTEN, p53 and p21, EGR-1 decreases cell proliferation, carrying out tumor suppressive functions in several tumor types including gliomas [10,11]. We observed that EGR-1 is less expressed in tumors and tumor-derived primary cell lines carrying wild type copies of p53 gene compared to those carrying p53 mutated copies [14]. We have asked whether variations in the constitutive expression of early-growth response factor 1 (EGR-1) predicted acute cytotoxicity and clonogenic cell death in vitro, induced by six different chemotherapics

Methods

Results

Discussion

Conclusion