1. Bone morphogenetic proteins-2 and -4 attenuate apoptosis in a cerebellar primitive neuroectodermal tumor cell line.
- Author
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Iantosca MR, McPherson CE, Ho SY, and Maxwell GD
- Subjects
- Bone Morphogenetic Protein 2, Bone Morphogenetic Protein 4, Bone Morphogenetic Protein 6, Bone Morphogenetic Protein Receptors, Cell Count drug effects, Cell Division drug effects, Cell Nucleus drug effects, Cell Nucleus metabolism, Cerebellum drug effects, DNA Fragmentation drug effects, Dose-Response Relationship, Drug, Ectoderm drug effects, Glial Cell Line-Derived Neurotrophic Factor, Humans, Nerve Tissue Proteins pharmacology, Proliferating Cell Nuclear Antigen metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, Cell Surface genetics, Transforming Growth Factor beta pharmacology, Tumor Cells, Cultured, Apoptosis drug effects, Bone Morphogenetic Proteins pharmacology, Cerebellum cytology, Ectoderm cytology, Nerve Growth Factors, Receptors, Growth Factor
- Abstract
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.
- Published
- 1999
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