Differential expression of HOX genes in neoplastic and non-neoplastic human astrocytes

Abstract

HOX genes are a large family of regulatory genes implicated in the control of developmental processes. HOX genes are involved in malignant transformation and progression of different types of tumour. Despite intensive efforts to delineate the expression profiles of HOX genes in other cell types, nothing is known regarding the global expression profile of these genes in normal human astrocytes and astrocytomas. The present study has analysed the expression profile of the 39 class I HOX genes in normal human astrocytes (NHA and E6/E7), two well-established glioblastoma cell lines (U-87 MG and U-1242-MG), as well as neoplastic (WHO grades II/III and IV) and non-neoplastic temporal lobe specimens with hippocampal sclerosis and medically intractable epilepsy. RT-PCR, quantitative real-time PCR, immunocytochemistry, and western blot analyses revealed differential expression of nine HOX genes (A6, A7, A9, A13, B13, D4, D9, D10, and D13) in normal human astrocytic cell lines and non-neoplastic temporal lobe specimens. The data show that HOX genes are differentially expressed in neoplastic and non-neoplastic astrocytes and that multiple HOX genes are overexpressed in glioblastoma cell lines, astrocytomas (II/III), and glioblastoma multiforme. The differential expression of HOX genes in normal and neoplastic astrocytes suggests a role for these genes in brain tumourigenesis.