Bone morphogenetic proteins-2 and -4 attenuate apoptosis in a cerebellar primitive neuroectodermal tumor cell line.
Similarities between primitive neuroectodermal tumors and central nervous system (CNS) progenitor cells have evoked interest in the response of these tumors to endogenous growth factors. The bone morphogenetic proteins (BMPs) have recently been found to regulate survival and differentiation of CNS progenitor cell populations. In this study, we investigated the effects of BMP-2, BMP-4, and BMP-6 on the undifferentiated cerebellar primitive neuroectodermal tumor or medulloblastoma cell line DAOY. Analysis by reverse transcriptase-polymerase chain reaction showed that mRNAs for type IA and type II BMP receptors were present in control cultures. In cultures treated with BMP-2, mRNAs for BMP receptor type IB and the activin R-I receptor became evident. Cultures were analyzed for total cell counts, proliferating cell nuclear antigen (PCNA), and apoptotic DNA fragmentation. There was a significant increase in total cell number in the BMP-2 and BMP-4 treatment groups, without any change in PCNA reactivity, and a dramatic decrease in the proportion of apoptotic nuclei at concentrations of BMP-2 and BMP-4 above 5 ng/ml (P<0.001). These effects were not observed with BMP-6, TGF-beta1 or GDNF. These results suggest that the increase in total cell number is due to the attenuation of apoptosis by BMP-2 and BMP-4. The anti-apoptotic effect of BMP-2 and BMP-4 on this neuroectodermal cell line has potential clinical implications for neuroectodermal tumors.
Iantosca
M R
MR
Division of Neurosurgery, University of Connecticut Health Center, Farmington 06030-3405, USA.
McPherson
C E
CE
Ho
S Y
SY
Maxwell
G D
GD
D017209:Apoptosis / Q000187:drug effects*; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004475:Ectoderm / Q000166:cytology* / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525816:BMP6 protein, human; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D052004:Bone Morphogenetic Protein Receptors