Increased Content of Neuropeptide Y in Human Pheochromocytoma Cell Cultures*

Tischler, Arthur S.; Allen, Janet M.; Costopoulos, Donna; Bloom, Stephen R.

doi:10.1210/jcem-61-2-303

Cited by 12 publications

(15 citation statements)

References 11 publications

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“…NGF increased NPY mRNA expression in primary cultures of pheochromocytoma cells. This seems to be in contrast to a previous report where NGF did not increase the cellular content of NPY after long-term incubation (13). However, in that study, the long-term (21 days) culture without any additives induced spontaneous neuronal differentiation with process outgrowth and high levels of immunoreactive NPY.…”

Section: Discussioncontrasting

confidence: 99%

“…NGF is able to induce differentiation of human pheochromocytoma cells to sympathetic neuron-like cells (13,17). Therefore, we used NGF to treat cultured pheochromocytoma cells.…”

Section: Discussionmentioning

confidence: 99%

“…However, in that study, the long-term (21 days) culture without any additives induced spontaneous neuronal differentiation with process outgrowth and high levels of immunoreactive NPY. NGF may not be able to further increase NPY gene expression in these conditions (13). Therefore, we used a relatively short-term (5-10 days) culture system to clarify if NGF could accelerate chromaffin cell differentiation and NPY mRNA accumulation.…”

Section: Discussionmentioning

confidence: 99%

“…However, differences may exist between human and rat PC12 pheochromocytoma cells in the regulation of NPY expression. For example, NPY peptide was not detected in the conditioned medium of human pheochromocytoma cells, long-term treatment with NGF did not increase NPY in human cells, and induction of the chromaffin phenotype by dexamethasone decreased NPY content in human pheochromocytoma cells (13). To shed more light on the regulation of NPY expression in human pheochromocytomas, we measured NPY mRNA expression in these tumors by Northern blot hybridization, and examined the effects of several differentiating agents on NPY gene expression in primary cultures of human pheochromocytoma cells.…”

Section: Introductionmentioning

confidence: 94%

“…The well-established rat pheochromocytoma PC12 cell line increased in NPY mRNA and cellular peptide levels during nerve growth factor (NGF)-or dexamethasone-induced differentiation, but no change in NPY concentration in the conditioned media was detected (11,12). Cultured human pheochromocytoma cells had a higher NPY content than freshly dissociated cells from the same tumors (13). Since the in vitro condition also promoted neuron-like differentiation, it appeared that the environment favoring expression of the neuronal phenotype also favored NPY production in human pheochromocytoma cells.…”

Section: Introductionmentioning

confidence: 98%

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Regulation of neuropeptide Y mRNA expression in cultured human pheochromocytoma cells

Liu

Kahri

Heikkilä

et al. 1999

European Journal of Endocrinology

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The expression of the neuropeptide Y (NPY) gene varies considerably in human pheochromocytomas, but the mechanisms for this variation have not been clarified. To investigate the regulation pattern of the NPY gene in human pheochromocytomas, we screened 16 pheochromocytomas and 9 normal adrenal tissues with Northern blots. The expression level of NPY mRNA in normal adrenal medulla was low and relatively constant, while the pheochromocytomas showed a very wide variation in NPY mRNA levels in both malignant and benign tumors. This indicates that NPY gene expression is not correlated with malignancy in pheochromocytomas. In primary cultures of human pheochromocytoma cells, nerve growth factor treatment (causing neuronal differentiation) increased NPY mRNA accumulation 2-to 5-fold (P < 0:05). NPY mRNA levels were also induced by protein kinase modulators (Bu) 2 cAMP and staurosporine in the cultures (P < 0:05). In contrast, treatment with dexamethasone and IGF-II (causing or linked with chromaffin differentiation) reduced NPY mRNA accumulation (P < 0:05). These data show that the regulation pattern of NPY mRNA expression in cultured human pheochromocytoma cells is different from that previously described in rat pheochromocytoma PC12 cells. Regulation of NPY mRNA expression in primary cultures by these differentiating factors suggests that the expression of NPY mRNA in pheochromocytoma tissues may be associated with the neuronal differentiation of the tumor cells affected by multiple factors.

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Section: Discussioncontrasting

confidence: 99%

“…NGF is able to induce differentiation of human pheochromocytoma cells to sympathetic neuron-like cells (13,17). Therefore, we used NGF to treat cultured pheochromocytoma cells.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

Regulation of neuropeptide Y mRNA expression in cultured human pheochromocytoma cells

Liu

Kahri

Heikkilä

et al. 1999

European Journal of Endocrinology

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Morphologic and biochemical variability of tissue and cultured cells from human pheochromocytoma

Jaques

Tobes

1986

Journal Cellular Physiology

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Primary cell cultures from 18 human pheochromocytomas were maintained in culture for 10 to 12 days and characterized. The cell yields ranged from 1.0 to 60.1 X 10(6) cells/g wet weight of tissue. Cell size, as determined by histofluorescent microscopy, varied as much as seven-fold among cells derived from a given tumor and ten-fold between cells from all tumors. Cell catecholamine content, norepinephrine (NE) plus epinephrine, ranged from 0.4 to 89.5 nmol/10(6) cells at day 5 in culture and did not correlate with catecholamine content of the tissue from which the cells were obtained. Cell catecholamine content decreased with time in culture, but this decrease could not be related to a change in cell viability, the type of media used, an inability to convert dopamine to NE, or an alteration in the uptake of 3H-NE. Cellular uptake of 1.0 microM 3H-NE varied as much as 230-fold between all cell dispersions. The basal and acetylcholine stimulated release of both preloaded 3H-NE and the endogenous catecholamines was quite variable. There was no correlation between the release rate, either basal or stimulated, of preloaded 3H-NE and the endogenous catecholamines. This study represents the largest existing data base on culturing cells from these tumors and describes many of the morphologic and biochemical characteristics of this cell system.

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Plasma gut hormone levels in 37 patients with pheochromocytomas

1986

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Pheochromocytomas are usually recognized by the effects of overproduction of catecholamines, but there are clinical features that cannot be ascribed to catecholamine excess that may be due to vasoactive peptides. We, therefore, measured blood levels of vasoactive intestinal peptides (VIP), substance P, somatostatin (SS), and motifin in 50 instances in 37 patients with pheochromocytomas-21 malignant, 10 benign intra-adrenal, and 6 ectopic (5 paracardial and 1 perirenal). Hormone levels were considered raised if the level was more than 3 S.D. above the mean value found in 52 healthy subjects. Of the 37 patients, 20 (54%) had an abnormality in 1 or more gut hormone levels. The most common abnormality was a raised SS in 9/37 (24%). In addition to these, however, 3 (8%) others had raised VIP, 5 (13.5%) raised motilin, and 3 (8%) raised substance P. Patients with benign adrenal adenomas had raised levels of SS and substance P. Ectopic pheochromocytomas produced only SS in addition to catecholamines, but malignant pheochromocytomas could secrete all 4 peptides, and more than 1 in the same patient. We conclude that pheochromocytomas may secrete multiple vasoactive peptides, and they are more likely to do so if malignant. Somatostatin is the most commonly secreted peptide and is found with benign adrenal and ectopic (paracardiac) tumors. If the level of more than 1 peptide is elevated, the likelihood of malignancy is significantly increased.

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Increased Content of Neuropeptide Y in Human Pheochromocytoma Cell Cultures*

Cited by 12 publications

References 11 publications

Regulation of neuropeptide Y mRNA expression in cultured human pheochromocytoma cells

Regulation of neuropeptide Y mRNA expression in cultured human pheochromocytoma cells

Morphologic and biochemical variability of tissue and cultured cells from human pheochromocytoma

Plasma gut hormone levels in 37 patients with pheochromocytomas

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