Bone morphogenetic proteins-2 and -4 attenuate apoptosis in a cerebellar primitive neuroectodermal tumor cell line

Mark R. Iantosca, Clifton E. McPherson, Shih Yieh Ho, Gerald D. Maxwell

Research output: Contribution to journalArticle

31 Citations (Scopus)

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-β1 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.

Original languageEnglish (US)
Pages (from-to)248-258
Number of pages11
JournalJournal of Neuroscience Research
Volume56
Issue number3
DOIs
StatePublished - May 1 1999

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Bone Morphogenetic Protein 4
Primitive Neuroectodermal Tumors
Bone Morphogenetic Protein 2
Tumor Cell Line
Apoptosis
Type I Bone Morphogenetic Protein Receptors
Bone Morphogenetic Protein 6
Cell Count
Proliferating Cell Nuclear Antigen
Type II Bone Morphogenetic Protein Receptors
Stem Cells
Central Nervous System
Neuroectodermal Tumors
Nervous System Neoplasms
Glial Cell Line-Derived Neurotrophic Factor
Cell Line
Activins
Messenger RNA
Bone Morphogenetic Proteins
Medulloblastoma

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

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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-β1 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.",
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Bone morphogenetic proteins-2 and -4 attenuate apoptosis in a cerebellar primitive neuroectodermal tumor cell line. / Iantosca, Mark R.; McPherson, Clifton E.; Ho, Shih Yieh; Maxwell, Gerald D.

In: Journal of Neuroscience Research, Vol. 56, No. 3, 01.05.1999, p. 248-258.

Research output: Contribution to journalArticle

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