Expression of the preproenkephalin A gene in tumor cells and brain glioma: A Northern and in situ hybridization study

Rost, Nathalie; Chaffanet, Max; Nissou, Marie-France; Chauvin, Christiane; Foote, Arthur; Lainé, Michèle G.; Benabid, Alim Louis

doi:10.1016/0143-4179(89)90010-3

Cited by 4 publications

(2 citation statements)

References 16 publications

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“…This and other evidence have prompted speculation that POMC expression is inhibited by factors that increase with progressive maturation, such as those provided by through afferent and/or efferent synaptic connections. Similarly, in a tumor cell model, the expression (derepression) of proenkephalin mRNA by rat C6 glioma cells in vitro 53 is reported to not be due to amplification of the proenkephalin gene during malignant transformation 40 , but is postulated to be due to the loss of feed-back inhibition by an external signal 40 .…”

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Cellular localization of proenkephalin mRNA and enkephalin peptide products in cultured astrocytes

et al. 1990

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To identify the possible cellular sites of opioid gene expression during ontogeny, proenkephalin mRNA and enkephalin peptide expression were examined, respectively, by in situ hybridization and immunocytochemistry in organotypic explants of rat cerebellum and in astrocyte-enriched cultures of murine cerebral hemispheres. High levels of proenkephalin mRNA and enkephalin immunoreactivity were detected in immature cells identified as astrocytes. Double-labeling studies combining in situ hybridization and immunocytochemical localization of the astrocytic marker, glial fibrillary acidic protein, provided direct evidence that proenkephalin mRNA is expressed by astrocytes in culture. Based on previous studies that Met-enkephalin can inhibit astrocyte growth in vitro, the present results suggest that proenkephalin gene expression by astrocytes is important during central nervous system maturation. KeywordsNeural development; In situ hybridization; Endogenous opioids; Proenkephalin A; Glial fibrillary acidic protein; Astrocyte; In vitroThe growth of neuronal and non-neuronal cells of the postnatal rat cerebral cortex, hippocampus, and cerebellum is modified by experimental manipulation of endogenous opioid systems (i.e, endogenous opioids and opioid receptors). Cellular differentiation 17,18 , cell number and packing density 54,55 , and cortical thickness 54,55 are modifiable by treatment with opioid antagonist drugs in vivo. In the cerebellum, [ 3 H]-thymidine incorporation by neuroblasts of the external granular layer (EGL) in 6-day-old rats is inhibited by systemic administration of Met-enkephalin, while treatment with the opioid antagonist naltrexone, at dosages sufficient to completely block opioid receptors, is reported to increase [ 3 H]-thymidine incorporation compared to untreated controls 56 . These and other experiments suggest that endogenous opioids are normally available to cells in the developing CNS in sufficient quantities to tonically inhibit growth 17,18,41,[54][55][56] . In support of this hypothesis, opioid peptide levels and opioid binding are greatly increased in the rat cerebellum 48,49 28,32,43,52 . In the present study, proenkephalin (proenkephalin A) mRNA and enkephalin peptide expression were examined by in situ hybridization and immunocytochemistry, respectively, in primary cultures of the developing CNS (i) to identify the specific cellular sites of proenkephalin gene and peptide expression, and (ii) to determine whether opioids are expressed by replicating astrocytes prior to their reaching confluence. We were particularly interested in determining whether rapidly dividing cells in astrocyte-enriched cultures express the proenkephalin gene prior to reaching confluence, because we have recently found that the proenkephalin peptide product, Met-enkephalin, selectively inhibits type 1 astrocyte proliferation at this time (i.e., at 4 or 6 days in vitro) 46,47 . Initial studies localized high levels of proenkephalin mRNA in cells with astrocytic morphology irrespective of culture conditi...

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Cellular localization of proenkephalin mRNA and enkephalin peptide products in cultured astrocytes

et al. 1990

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“…C6 cells, both in culture and in implant-derived tumors, have been found to express high levels of preproenkephalin mRNA relative to normal brain (Rost et al, 1989). Met-enkephalin (a product of the preproenkephalin gene) has been described as a malignancy marker for neuroectodermal tumors such as gliomas, however, an inverse correlation between the level of Met-enkephalin and the degree of malignancy was observed (Gustin et al, 1993).…”

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Growth and migration markers of rat C6 glioma cells identified by serial analysis of gene expression

Gunnersen

Spirkoska

Smith

et al. 2000

Glia

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Differential effects of methionine enkephalin on the growth of brain tumor cells

Lee

Wurster

1994

J Neuro-Oncol

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The effect of methionine enkephalin on the growth of human brain tumor cells was investigated. The results show that this endogenous opioid has dual effects on tumor cell growth. This peptide exerted an inhibitory effect in SK-N-MC human neuroblastoma cell line; in contrast, in U-373 MG human astrocytoma cell line, the peptide showed a stimulatory effect. Treatment with naltrexone, an opioid receptor antagonist, also resulted in a similar alteration of tumor cell growth implicating that its action may be unrelated to opioid receptor blockade. These results suggest that in these tumor cell lines endogenous opioid systems may be involved in cell proliferation. Furthermore, these tumor cell lines may be useful model systems for the study of the signal transduction mechanisms of endogenous opioids.

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Expression of the preproenkephalin A gene in tumor cells and brain glioma: A Northern and in situ hybridization study

Cited by 4 publications

References 16 publications

Cellular localization of proenkephalin mRNA and enkephalin peptide products in cultured astrocytes

Cellular localization of proenkephalin mRNA and enkephalin peptide products in cultured astrocytes

Growth and migration markers of rat C6 glioma cells identified by serial analysis of gene expression

Differential effects of methionine enkephalin on the growth of brain tumor cells

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