Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumours.
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.
Miracco
Clelia
C
Department of Human Pathology and Oncology, Section of Pathological Anatomy, University of Siena, I-53100 Siena, Italy. miracco@unisi.it
Cosci
Elena
E
Oliveri
Giuseppe
G
Luzi
Pietro
P
Pacenti
Lorenzo
L
Monciatti
Irene
I
Mannucci
Susanna
S
De Nisi
Maria Caterina
MC
Toscano
Marzia
M
Malagnino
Valeria
V
Falzarano
Sara M
SM
Pirtoli
Luigi
L
Tosi
Piero
P
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
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D012333:RNA, Messenger