Comparative Studies of Pc12 and Mouse Pheochromocytoma–derived Rodent Cell Lines as Models for the Study of Neuroendocrine Systems

Dixon, Darcelle N.; Loxley, Rhonda A.; Barron, Anna M.; Cleary, Susannah; Phillips, Jacqueline K.

doi:10.1290/0411077.1

Cited by 24 publications

(19 citation statements)

References 42 publications

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“…In addition to the PC12 cell line model described above, we also used the MPC cell line model to further explore the role of MAX expression in chromaffin cell differentiation. As MPC cells express PNMT and produce epinephrine, this provides some advantages for their use in studies of chromaffin cell differentiation over PC12 cells, which express negligible PNMT and produce little epinephrine …”

Section: Resultsmentioning

confidence: 99%

“…As MPC cells express PNMT and produce epinephrine, this provides some advantages for their use in studies of chromaffin cell differentiation over PC12 cells, which express negligible PNMT and produce little epinephrine. 27 Using siRNA specifically targeted to Max, an 80% reduction of Max mRNA was evident 48 hr after transfection (Supporting Information Fig. S1a).…”

Section: Max Modulates Expression Of the Chromaffin Cell Differentiatmentioning

confidence: 98%

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Opposing effects of HIF1α and HIF2α on chromaffin cell phenotypic features and tumor cell proliferation: Insights from MYC‐associated factor X

Qin

Cubas

García‐Martín

et al. 2014

Intl Journal of Cancer

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Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing chromaffin cell tumors with diverse phenotypic features reflecting mutations in numerous genes, including MYC-associated factor X (MAX). To explore whether phenotypic differences among PPGLs reflect a MAX-mediated mechanism and opposing influences of hypoxia-inducible factor (HIF)s HIF2a and HIF1a, we combined observational investigations in PPGLs and gene-manipulation studies in two pheochromocytoma cell lines. Among PPGLs from 140 patients, tumors due to MAX mutations were characterized by gene expression profiles and intermediate phenotypic features that distinguished these tumors from other PPGLs, all of which fell into two expression clusters: one cluster with low expression of HIF2a and mature phenotypic features and the other with high expression of HIF2a and immature phenotypic features due to mutations stabilizing HIFs. Max-mutated tumors distributed to a distinct subcluster of the former group. In cell lines lacking Max, re-expression of the gene resulted in maturation of phenotypic features and decreased cell cycle progression. In cell lines lacking Hif2a, overexpression of the gene led to immature phenotypic features, failure of dexamethasone to induce differentiation and increased proliferation. HIF1a had opposing actions to HIF2a in both cell lines, supporting evolving evidence of their differential actions on tumorigenic processes via a MYC/MAX-related pathway. Requirement of a fully functional MYC/MAX complex to facilitate differentiation explains the intermediate phenotypic features in tumors due to MAX mutations. Overexpression of HIF2a in chromaffin cell tumors due to mutations affecting HIF stabilization explains their proliferative features and why the tumors fail to differentiate even when exposed locally to adrenal steroids.

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Section: Resultsmentioning

confidence: 99%

Section: Max Modulates Expression Of the Chromaffin Cell Differentiatmentioning

confidence: 98%

Opposing effects of HIF1α and HIF2α on chromaffin cell phenotypic features and tumor cell proliferation: Insights from MYC‐associated factor X

Qin

Cubas

García‐Martín

et al. 2014

Intl Journal of Cancer

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“…Each bead secreted 460 pg/day of norepinephrine by ELISA. Dopamine levels in PC12 cells were undetectable30, as were epinephrine levels given the low or non-existent expression of phenylethanolamine-N-methyltransferase, the enzyme responsible for converting norepinephrine to epinephrine31.The lack of epinephrine or dopamine secretion makes these cells then an ideal side-by-side comparison to the NE-secreting pumps.…”

Section: Methodsmentioning

confidence: 99%

Pheochromocytoma-Induced Cardiomyopathy is Modulated by the Synergistic Effects of Cell-Secreted Factors

Mobine

Baker

Wang

et al. 2009

Circ: Heart Failure

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Background-Pheochromocytomas are rare tumors derived from the chromaffin cells of the adrenal medulla. Although these tumors have long been postulated to induce hypertension and cardiomyopathy through the hypersecretion of catecholamines, catecholamines alone may not fully explain the profound myocardial remodeling induced by these tumors. We sought to determine whether changes in myocardial function in pheochromocytoma-induced cardiomyopathy result solely from catecholamines secretion or from multiple pheochromocytoma-derived factors. Methods and Results-Isolated cardiomyocytes incubated with pheochromocytoma-conditioned growth media contracted at a higher frequency than cardiomyocytes incubated with norepinephrine (NE) only. Sprague-Dawley rats and black-6 mice were implanted with agarose-encapsulated pheochromocytoma (PC12) cells, dihydroxyphenylalanine decarboxylase knock-out PC12 cells deficient in NE (PC12-KO), or NE-secreting pumps. PC12 cell implantation increased left ventricular dilation by 35Ϯ6% and 9.6Ϯ1.4% and reduced left ventricular fractional shortening by 20Ϯ3% and 28Ϯ4% in rats and mice compared with animals dosed only with NE, respectively. Elimination of NE secretion in PC12-KO cells induced neither cardiac dilation (3.9%Ϯ1.8% increase versus control) nor changes in (1.9%Ϯ0.4% reduction) fractional shortening compared to controls. Conclusions-Pheochromocytomas induce a greater degree of cardiomyopathy than equivalent doses of NE, suggesting pheochromocytoma-induced cardiomyopathy is not solely mediated by NE, rather pheochromocytoma secretory factors in combination with catecholamines act synergistically to induce greater cardiac damage than catecholamines alone.

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“…The cell suspension was again centrifuged at 1000 rpm for 5 min. The supernatant was discarded and the cells were resuspended in Roswell Park Memorial Institute (RPMI) medium [13]. The cells were then counted using a Neubar's Chamber TM (Fisher Scientific, Pittsburgh, PA, USA).…”

Section: Pheocromocytoma Cells (Pc 12)mentioning

confidence: 99%

Performance tests of a novel coaxial tube catheter in anin vitromodel of intracranial cell delivery

Panse¹,

Fillmore²,

Chen³

et al. 2011

Journal of Medical Engineering & Technology

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We have tested prototypes of a novel coaxial tube catheter in an in vitro gel model of cell delivery into the brain. Devices 1.6 and 2.0 mm outer diameter were used to deliver PC 12 cells (concentration = 10⁶ cells ml⁻¹ at 1 μl min⁻¹ into a 5 ml sandwich of collagen and 0.1% agarose, with and without follow-on infusions of nerve growth factor (NGF). Post-infusion microscopic imaging (40X) at the infusion sites was then carried out over 7-day periods. The results showed that under these experimental conditions, it was possible to use these catheters to deliver cells without either leakage of trapped air into the gel or reflux of the cell suspension along the catheter insertion track. Differentiation of the NGF-treated cells was observed.

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Comparative Studies of Pc12 and Mouse Pheochromocytoma–derived Rodent Cell Lines as Models for the Study of Neuroendocrine Systems

Cited by 24 publications

References 42 publications

Opposing effects of HIF1α and HIF2α on chromaffin cell phenotypic features and tumor cell proliferation: Insights from MYC‐associated factor X

Opposing effects of HIF1α and HIF2α on chromaffin cell phenotypic features and tumor cell proliferation: Insights from MYC‐associated factor X

Pheochromocytoma-Induced Cardiomyopathy is Modulated by the Synergistic Effects of Cell-Secreted Factors

Performance tests of a novel coaxial tube catheter in anin vitromodel of intracranial cell delivery

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