ABSTRACT
Cyclin D2, P53, Rb and ATM as cell cycle genes regulate cell growth and proliferation. Considering their roles, we assumed that they have different level of mRNA expression in different grades of brain tumors. To determine this point, we investigated the mRNA expression in two types of brain tumors, including astrocytoma and meningioma. The mRNA of 52 brain tumor samples were extracted; cyclin D2, P53, Rb and ATM mRNA expression was quantified using the real-time quantitative reverse-transcription polymerase chain reaction. We compared mRNA expression of these genes between astrocytoma and meningioma tumors and also between different grades of them. Cyclin D2, P53, Rb and ATM had higher expression in astrocytoma than meningioma tumors. Higher grade (III and IV) of astrocytoma tumors had up-regulation for cyclin D2 and ATM genes, but higher grades of these tumors showed down-regulation of P53 and Rb genes. Analysis of relative expression between two grades of meningioma tumors showed a high down-regulation in grade II related to grade I. Also, cyclin D2, P53, Rb and ATM mRNA expression in each group of tumors (meningioma and astrocytoma) showed a highly positive correlation in lower grades. Considering this fact and also different templates of up- and down-regulation for these genes' interaction in different types of brain tumors, it seems that these genes do not have a unique model of interaction.
Subject(s)
Astrocytoma/genetics , Brain Neoplasms/genetics , Cell Cycle Proteins/genetics , Cyclin D2/genetics , DNA-Binding Proteins/genetics , Meningioma/genetics , Protein Serine-Threonine Kinases/genetics , Retinoblastoma Protein/genetics , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Proteins/genetics , Adult , Astrocytoma/metabolism , Astrocytoma/surgery , Ataxia Telangiectasia Mutated Proteins , Brain Neoplasms/metabolism , Brain Neoplasms/surgery , Cell Cycle Proteins/metabolism , Cyclin D2/metabolism , DNA-Binding Proteins/metabolism , Female , Humans , Male , Meningioma/metabolism , Meningioma/surgery , Middle Aged , Prognosis , Protein Serine-Threonine Kinases/metabolism , RNA, Messenger/genetics , Retinoblastoma Protein/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Proteins/metabolismABSTRACT
Ataxia telangictasia mutated (ATM) is involved in DNA repair pathway and cell-cycle checkpoints. ATM alterations were found in medulloblastomas, gliomas, but not in astrocytoma. The polymorphism D1853N was reported in healthy individuals and medulloblastomas. We could observe this polymorphism, heterozygously, in a proband affected with astrocytoma and traced it through her pedigree. We propose the three-hit hypothesis as a triangle initiators includes D1853N as a first predisposing hit, IVS 38- 63T --> A as a second hit deriving from the first somatic evolution before differentiation and IVS 38- 30 A --> G as a third hit through the development of an astrocytoma. In addition, the D1853N polymorphism was occurred in different allele from IVS 38- 63T --> A and IVS 38- 30 A --> G.
