title: Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumours.
abstract: Beclin 1 is is an autophagy gene, the role of which as a tumour suppressor has recently been recognized in a few studies. We examined the expression of Beclin 1 protein in 212 primary human brain tumours, including 97 high-grade glial tumours, 29 low-grade glial tumours, 4 grade III meningiomas, 19 grade II meningiomas, 52 grade I meningiomas, and 11 medulloblastomas. In 94 cases, including 56 glial tumours, 35 meningiomas, and 3 medulloblastomas we also assessed Beclin 1 mRNA expression by real-time RT-PCR. In most high-grade astrocytic, ependymal neoplasms and atypical meningiomas we found a decrease of cytoplasmic protein expression that was, instead, high in the majority of low-grade tumours and in medulloblastomas. The expression level of Beclin 1 mRNA was significantly lower in glioblastomas than in grade II (p=0.04) and grade I (p=0.01) astrocytomas; in grade III than in grade I astrocytomas (p=0.01); in grade II than in grade I meningiomas (p=0.03); and in all glial tumours when compared to all meningiomas (p<0.0001). Cytoplasmic expression is thought to be linked to the functional protein. Our observations are in line with studies that demonstrated decreased expression of Beclin 1 in human breast, ovarian, prostate and ovarian cancer and furtherly support its involvement also in brain tumours, which had previously been demonstrated in a few experimental studies, both in spontaneous and in therapy-induced autophagy. Furthermore, our study suggests possible differences of Beclin 1 involvement and its role among the different histotypes of brain neoplasms. Further studies are needed to highlight Beclin 1 function in tumour suppression and/or in tumour survival through autophagy and other related programmed cell death processes in brain tumours.
authors.affiliation: Department of Human Pathology and Oncology, Section of Pathological Anatomy, University of Siena, I-53100 Siena, Italy. miracco@unisi.it
authors.forename: Clelia
authors.initials: C
authors.lastname: Miracco
authors.forename: Elena
authors.initials: E
authors.lastname: Cosci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Oliveri
authors.forename: Pietro
authors.initials: P
authors.lastname: Luzi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pacenti
authors.forename: Irene
authors.initials: I
authors.lastname: Monciatti
authors.forename: Susanna
authors.initials: S
authors.lastname: Mannucci
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: De Nisi
authors.forename: Marzia
authors.initials: M
authors.lastname: Toscano
authors.forename: Valeria
authors.initials: V
authors.lastname: Malagnino
authors.forename: Sara M
authors.initials: SM
authors.lastname: Falzarano
authors.forename: Luigi
authors.initials: L
authors.lastname: Pirtoli
authors.forename: Piero
authors.initials: P
authors.lastname: Tosi
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000502:physiology; D001343:Autophagy; D000071186:Beclin-1; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008527:Medulloblastoma / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000502:physiology; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology; D009837:Oligodendroglioma / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D012333:RNA, Messenger