Notch Signaling in Human Neuroblastoma Cells
(2005) In Lund University Faculty of Medicine Doctoral Dissertation Series- Abstract
- Neuroblastoma is a childhood tumor derived from the sympathetic nervous system (SNS). It is believed that the tumors arise from cells halted in their differentiation and due to their immature phenotype; they express proteins normally only detected during embryogenesis. One such protein is Hash-1, which is required for formation of the SNS. Hash-1 is a component of the Notch signaling cascade, which is involved in many cell fate decisions. In general, Notch activity maintains a pool of undifferentiated cells and dysregulated Notch signaling has been linked to development of several cancers. It has been shown that the Notch cascade is transiently induced during neuroblastoma cell differentiation in vitro and that persistent Notch expression... (More)
- Neuroblastoma is a childhood tumor derived from the sympathetic nervous system (SNS). It is believed that the tumors arise from cells halted in their differentiation and due to their immature phenotype; they express proteins normally only detected during embryogenesis. One such protein is Hash-1, which is required for formation of the SNS. Hash-1 is a component of the Notch signaling cascade, which is involved in many cell fate decisions. In general, Notch activity maintains a pool of undifferentiated cells and dysregulated Notch signaling has been linked to development of several cancers. It has been shown that the Notch cascade is transiently induced during neuroblastoma cell differentiation in vitro and that persistent Notch expression inhibits this differentiation. These observations imply a role for Notch signaling in the blocked differentiation of neuroblastoma cells. In addition, neuroblastoma cells exposed to hypoxia, a common event of solid tumors, dedifferentiate. During this process, components of the Notch signaling cascade are up regulated. In this thesis we show that Hash-1 interacts with ubiquilin-1, a protein involved in protecting proteins from degradation. In addition, we show that valproic acid (VPA) induces differentiation of neuroblastoma cells by modulation of the Notch signaling cascade. Aberrant signaling through the EGF receptor is involved in the genesis of some human cancers. Several reports have shown cross talk between EGFR signaling and the Notch cascade. We show here that the Notch target Hes-1 can be directly regulated by Ras/MAPK signaling at both normoxia and hypoxia, without the activation of Notch receptors. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/545191
- author
- Stockhausen, Marie LU
- supervisor
- opponent
-
- Professor Versteeg, Rogier, Department of Human Genetics, University of Amsterdam, The Netherlands
- organization
- publishing date
- 2005
- type
- Thesis
- publication status
- published
- subject
- keywords
- oncology, Hes-1, Medicin (människa och djur), Medicine (human and vertebrates), hypoxia, TGF-alpha, EGFR, ERK1/2, Ras/MAPK, differentiation, valproic acid, ubiquilin-1, neuroblastoma, Hash-1, Cytologi, onkologi, cancer, cancerology, Cytology, Notch
- in
- Lund University Faculty of Medicine Doctoral Dissertation Series
- pages
- 106 pages
- publisher
- Department of Laboratory Medicine, Lund University
- defense location
- Main Lecture Hall, Pathology Building, Entrance 78, 2nd floor, Malmö University Hospital, Malmö
- defense date
- 2005-09-16 09:15:00
- ISSN
- 1652-8220
- ISBN
- 91-85439-68-1
- language
- English
- LU publication?
- yes
- additional info
- Marie Stockhausen. 2004. Ubiquilin-1 is a novel HASH-1-complexing protein that regulates levels of neuronal bHLH transcription factors in human neuroblastoma cells International Journal of Oncology, vol 25 pp 1213-1221.Marie Stockhausen. 2005. Effects of the histone deacetylase inhibitor valproic acid on Notch signalling in human neuroblastoma cells British Journal of Cancer, vol 92 pp 751-759.Marie Stockhausen. 2005. Regulation of the Notch target gene Hes-1 by TGF-alpha induced Ras/MAPK signaling in human neuroblastoma cells Experimental Cell Research, (inpress)Marie Stockhausen. . Regulation of the Notch target Hes-1 by hypoxia in human neuroblastoma cells (manuscript)The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Molecular Medicine (013031200)
- id
- f9f7273b-4d37-4247-b9e4-2fbf08f4a6bb (old id 545191)
- date added to LUP
- 2016-04-01 15:40:45
- date last changed
- 2019-05-21 21:45:39
@phdthesis{f9f7273b-4d37-4247-b9e4-2fbf08f4a6bb, abstract = {{Neuroblastoma is a childhood tumor derived from the sympathetic nervous system (SNS). It is believed that the tumors arise from cells halted in their differentiation and due to their immature phenotype; they express proteins normally only detected during embryogenesis. One such protein is Hash-1, which is required for formation of the SNS. Hash-1 is a component of the Notch signaling cascade, which is involved in many cell fate decisions. In general, Notch activity maintains a pool of undifferentiated cells and dysregulated Notch signaling has been linked to development of several cancers. It has been shown that the Notch cascade is transiently induced during neuroblastoma cell differentiation in vitro and that persistent Notch expression inhibits this differentiation. These observations imply a role for Notch signaling in the blocked differentiation of neuroblastoma cells. In addition, neuroblastoma cells exposed to hypoxia, a common event of solid tumors, dedifferentiate. During this process, components of the Notch signaling cascade are up regulated. In this thesis we show that Hash-1 interacts with ubiquilin-1, a protein involved in protecting proteins from degradation. In addition, we show that valproic acid (VPA) induces differentiation of neuroblastoma cells by modulation of the Notch signaling cascade. Aberrant signaling through the EGF receptor is involved in the genesis of some human cancers. Several reports have shown cross talk between EGFR signaling and the Notch cascade. We show here that the Notch target Hes-1 can be directly regulated by Ras/MAPK signaling at both normoxia and hypoxia, without the activation of Notch receptors.}}, author = {{Stockhausen, Marie}}, isbn = {{91-85439-68-1}}, issn = {{1652-8220}}, keywords = {{oncology; Hes-1; Medicin (människa och djur); Medicine (human and vertebrates); hypoxia; TGF-alpha; EGFR; ERK1/2; Ras/MAPK; differentiation; valproic acid; ubiquilin-1; neuroblastoma; Hash-1; Cytologi; onkologi; cancer; cancerology; Cytology; Notch}}, language = {{eng}}, publisher = {{Department of Laboratory Medicine, Lund University}}, school = {{Lund University}}, series = {{Lund University Faculty of Medicine Doctoral Dissertation Series}}, title = {{Notch Signaling in Human Neuroblastoma Cells}}, url = {{https://lup.lub.lu.se/search/files/4447289/545192.pdf}}, year = {{2005}}, }