Neuroblastoma: Drug-Induced Differentiation Increases Proportion of Cytoplasmic RNA That Contains Polyadenylic Acid

Bondy, Stephen C.; Prasad, Kedar N.; Purdy, Janet L.

doi:10.1126/science.186.4161.359

Cited by 29 publications

(19 citation statements)

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“…Although PGE1 and R020-1724 induce many differentiated functions in neuroblastoma cells in a similar manner, (Furmanski, Silverman andLubin, 1971, Prasad andKumar, 1974) PGE1 appears to change characteristically the expression of AK and G6PD,6PGD and LDH. From these data it is clear that PGE1-treated neuroblastoma cells in culture express different enzyme patterns from those cells which were treated with R020-1724. Previous studies have shown that many differentiated functions in neuroblastoma cells are induced both by PGE1 andR020-1724 (Furmanski et al, 1971;Prasad and Kumar, 1974).…”

Section: In Vitro Systemmentioning

confidence: 99%

“…We have shown that the muscletype lactate dehydrogenase (LDH-5) which prevails in embryonic tissue (Wolf and Engel,1.972) is present in neuroblastoma cells, but absent from mouse brain tissue , indicating the re-expression of an embryonic feature during malignant transformation. In addition, it has been reported (Bondy, Prasad and Purdy, 1974) that the amount of poly-adenylic-(A)-containing cytoplasmic RNA is greater in cAMP-induced " differentiated" neuroblastoma cells than that in malignant cells. These data indicate that there may be an alteration in the expression of genetic information during the time of " differentiation " of neuroblastoma cells in culture.…”

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confidence: 99%

“…We now report the following: (a) several of the enzymes which are present in brain are absent in neuroblastoma cells in vivo and in vitro; Cell culture.-The procedure for culturing mouse neuroblastoma cells has been previously described by Prasad and Hsie (1971). Previously defined neuroblastoma clone NBA2 (Bondy et al, 1974) was used in this study. Neuroblastoma cells contain tyrosine hydroxylase and acetylcholinesterase activities, but have no choline acetyltransferase activity.…”

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confidence: 99%

“…AN ELEVATION of the initracellular level of cAMP in neuroblastoma cells in culture induces many differentiated functions which are characteristic of mature neurons. These include formation of long neurites, (Prasad and Hsie, 1971) increase in size of soma and nucleus associated with an increase in total RNA (Augusti-Tocco, et al, 1973; blockade of cells in Gl-phase of cell cycle, , increase in activities of tyrosine hydroxylase, (Richelson, 1973;Waymire, Weiner and Prasad, 1.972) choline acetyltransferase (Prasad and Mandal, 1973) and acetylcholinesterase, (Furmanski, Silverman and Lubin, 1971;Blume et al, 1970), loss of tumourigenicity (Prasad, 1972) and increase in sensitivity of adenylate cyclase to catecholamines (Prasad and Kumar, 1974). We have shown that the muscletype lactate dehydrogenase (LDH-5) which prevails in embryonic tissue (Wolf and Engel,1.972) is present in neuroblastoma cells, but absent from mouse brain tissue , indicating the re-expression of an embryonic feature during malignant transformation.…”

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confidence: 99%

“…Tumours were produced in male A/J mice by injecting cells of clones NBA2 (Bondy et al, 1974). The tumour was allowed to grow for 15 days.…”

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confidence: 99%

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Altered enzyme expression in ”differentiated” murine neuroblastoma cells

Prasad¹,

Prasad²

1976

Br J Cancer

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Summary.-Out of 17 enzymes studied, only 9 were detectable by starch gel electrophoresis in mouse neuroblastoma cells in culture. Prostaglandin E1 (PGE1) and 4(-3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724), a specific inhibitor of cAMP phosphodiesterase, were used to induce " differentiation ". Lactate and 6-phosphogluconate dehydrogenases and adenylate kinase were expressed as single bands in untreated neuroblastoma and induced " differentiated " cells, but the electrophoretic mobility of these enzymes in PGEl-treated cells was slower than that in malignant and R020-1724-treated cells. Three bands of glucose 6-phosphate dehydrogenase were detectable in PGEl-treated cells, whereas the R020-1724-treated cells had two bands and the untreated neuroblastoma cells had only one band. Aldolase was also expressed as a single band; however, the activity of this enzyme was much higher in PGEl-treated cells, whereas the activity was barely detectable for R020-1724-treated and untreated neuroblastoma cells. Some of the enzymes which are present in vivo are absent in vitro. Alkaline phosphatase is present in brain but is absent in neuroblastoma cells in vivo and in vitro. Two bands each of triose phosphate isomerase, fumarase and aldolase are present in brain, but only one band of these enzymes is present in neuroblastoma cells. Although PGE1 and R020-1724 induce many differentiated functions in neuroblastoma cells in a similar manner, PGE1 appears to change characteristically the expression of several enzymes.

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Section: In Vitro Systemmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

“…Tumours were produced in male A/J mice by injecting cells of clones NBA2 (Bondy et al, 1974). The tumour was allowed to grow for 15 days.…”

mentioning

confidence: 99%

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Altered enzyme expression in ”differentiated” murine neuroblastoma cells

Prasad¹,

Prasad²

1976

Br J Cancer

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Nerve growth factor and neural oncology

Vinores¹,

Perez‐Polo²

1983

J of Neuroscience Research

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The precise role of the nerve growth factor protein (NGF) during the growth and development of the human nervous system is not determined. Although it appears to influence a number of neural functions, its mechanism of action is poorly understood. A number of researchers have proposed that NGF may be involved in several pathological conditions including cancer. It has been shown that NGF is secreted by certain sarcoma (23), neuroblastoma (113), and glioma (7,102,136) cell lines and can bind to neuroblastoma and metastatic melanoma cell lines (42). Neuroblastoma (136,181) and pheochromocytoma (165) cells in vitro can be induced by NGF to differentiate toward a morphologically "more benign" state and appropriate NGF treatment of rats can reduce the number of chemically induced gliomas and neurinomas (174,178). NGF can also reduce the growth of intracerebrally inoculated anaplastic glioma cells (172). Anti-NGF treatment of rats (178) and mice (179) can alter the tumor distribution observed following ethylnitrosourea or benzo(a)pyrene treatment (10). In humans, it has been reported that serum levels of NGF are usually elevated in persons "at risk" for neurofibromatosis (156). The precise nature of the NGF role is not known in these instances. Further understanding of the action of NGF could be of clinical importance.

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