Ras-MAPK signaling in differentiating SH-SY5Y human neuroblastoma cells [Elektronisk resurs]
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Olsson, Anna-Karin (författare)
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Uppsala universitet Medicinska vetenskapsområdet (utgivare)
- Publicerad: Uppsala : Acta Universitatis Upsaliensis, 2000
- Engelska 66
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Serie: Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 0282-7476 0282-7476 ; 950
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Sammanfattning
Ämnesord
Stäng
- Neuroblastoma is a malignant childhood cancer, originating from sympathetic neuroblasts of the peripheral nervous system. Neuroblastoma is a heterogenous group of tumours, while some are highly malignant others can spontaneosly mature into a more benign form or regress. Less than half of the patients survive and this statistics has improved only modestly over the past 20 years. SH-SY5Y is a human neuroblastoma cell line established from a highly malignant tumour. The cells have retained a capacity to differentiate in vitro in response to low concentrations of the phorbolester 12-O-tetradecanoylphorbol-13-acetate (TPA) in the presence of serum or defined growth factors. Differentiated cells are characterised by neurite formation and upregulation of neuronal marker genes. SH-SY5Y are unresponsive to nerve growth factor (NGF), but when transfected to express the NGF-receptor TrkA, they differentiate in response to NGF. Protein kinase C (PKC) is pivotal for the differentiation response to take place. We have investigated the role of signaling through the Ras-MAPK pathway in differentiating SH-SY5Y, with respect to neurite formation, expression of neuronal marker genes and growth control. Our results show that differentiation-promoting treatment induced a sustained activation and nuclear accumulation of the MAPK ERK in SH-SY5Y. The nuclear accumulation of ERK was PKC-dependent. However, nuclear accumulation of ERK was not sufficient for a differentiation response to take place in these cells, but ERK activity was needed for the characteristic upregulation of NPY and GAP-43 induced by TPA. ERK activity did not induce neurite formation, neither was it necessary for TPA-induced neurite formation. Instead, stimulation of a pathway distinct from MEK/ERK, but downstream of Ras, was needed for morphological differentiation. We could also show that differentiated cells still entered S-phase and that there was no correlation between expression of the CKI p21 cip1 (an ERK target), BrdU-incorporation or neurite formation.
Ämnesord
- Medical and Health Sciences (hsv)
- Basic Medicine (hsv)
- Medical Genetics (hsv)
- Medicin och hälsovetenskap (hsv)
- Medicinska och farmaceutiska grundvetenskaper (hsv)
- Medicinsk genetik (hsv)
- MEDICINE (svep)
- Dermatology and venerology,clinical genetics, internal medicine (svep)
- Clinical genetics (svep)
- MEDICIN (svep)
- Dermatologi och venerologi, klinisk genetik, invärtesmedicin (svep)
- Klinisk genetik (svep)
- Pathology (uu)
- patologi (uu)
Genre
- government publication (marcgt)
Indexterm och SAB-rubrik
- Genetics
- Neuroblastoma
- SH-SY5Y
- differentiation
- neurite
- Ras
- MAPK
- PKC
- Genetik
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