Transcriptional networks in neuroblastoma and breast cancer

Christina Manetopoulos

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Transcription factors of the basic Helix-loop-helix (bHLH) family of proteins are important regulators of cellular processes such as proliferation and differentiation. Many cancer diseases show a block in differentiation, and aberrant regulation of several bHLH factors have been implicated in the development of different malignancies.

Neuroblastoma is a childhood tumour that arises in the developing sympathetic nervous system. The cells are blocked at an early stage of differentiation and display an immature phenotype. HEN1 is a bHLH transcription factor important for neuronal development originally isolated from neuroblastoma. We studied HEN1 and its functional interaction with the Lim-only (LMO) proteins in neuroblastoma. We detected a strong interaction between HEN1 and LMO4, and this interaction modulated the HEN1 transcription activity. Furthermore, we found a possible role for HEN1 in neuronal differentiation, however, the significance of this finding needs further experiments.

The O/E-protein family also share the HLH motif and functions in neuronal development. In our study on O/E-proteins, we discovered expression of these factors in neuroblastoma. We found that O/E-1 regulate the expression of the important neuronal marker genes SCG10 and Chromogranin A.

bHLH factors are also involved in the regulation of proper development of breast tissue. ID2 has been implicated in the development of breast cancer. We studied the ID2 expression in a breast cancer tissue array, where ID2 correlated with a less aggressive tumour phenotype.

Furthermore, we studied the relation between the important signalling pathways involving Notch1 and its target gene and ERK1/2 in breast cancer. The results revealed a Notch1-independent regulation of Hes1 and that ERK1/2 signalling might contribute to regulation of Hes1 expression in breast cancer.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Department of Translational Medicine
Supervisors/Advisors
  • Axelson, Håkan, Supervisor
Award date2007 Jan 18
Publisher
ISBN (Print)91-85559-74-1
Publication statusPublished - 2007

Bibliographical note

Defence details

Date: 2007-01-18
Time: 09:15
Place: Entrance 78, 2nd floor, Pathology lecture hall University Hospital MAS, Malmö

External reviewer(s)

Name: Åman, Pierre
Title: Professor
Affiliation: Department of Pathology, Gothenburg University, Sahlgrenska University Hospital, Sweden

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<div class="article_info">C Manetopoulos, A Hansson, J Karlsson, J.I Jönsson and H Axelson. <span class="article_issue_date">2003</span>. <span class="article_title">The Lim-only protein LMO4 modulates the transcriptional activity of HEN1.</span> <span class="journal_series_title">Biochem Biophys Res Commun.</span>, <span class="journal_volume">vol 307</span> <span class="journal_pages">pp 891-9</span>.</div>
<div class="article_info">P Persson, C Manetopoulos, J Nygren, R Gisler, H Axelson and M Sigvardson. <span class="article_issue_date">2004</span>. <span class="article_title">Olf/EBF Proteins are Expressed in Neuroblastoma Cells: Potential Regulators of the Chromogranin A and SCG10 Promoters.</span> <span class="journal_series_title">Int J Cancer</span>, <span class="journal_volume">vol 110</span> <span class="journal_pages">pp 22-30</span>.</div>
<div class="article_info">. <span class="article_issue_date">2005</span>. <span class="article_title">High ID2 protein expression correlates with a favourable prognosis in patients with primary breast cancer and reduces cellular invasiveness of breast cancer cells.</span> <span class="journal_series_title">Int J Cancer</span>, <span class="journal_volume">vol 115</span> <span class="journal_pages">pp 403-411</span>.</div>
<div class="article_info">M Stighall, C Manetopoulos, H Axelson and G Landberg. <span class="article_issue_date">2005</span>. <span class="article_title">High ID2 protein expression correlates with a favourable prognosis in patients with primary breast cancer and reduces cellular invasiveness of breast cancer cells.</span> <span class="journal_series_title">Int J Cancer</span>, <span class="journal_volume">vol 115</span> <span class="journal_pages">pp 403-411</span>.</div>
<div class="article_info">C Manetopoulos, S Svensson Månsson, M Johansson, G Landberg and H Axelson. <span class="article_issue_date"></span>. <span class="article_title">Association between the ERK pathway and the Notch target gene Hes1 in primary breast cancer and in breast cancer cell lines.</span> (submitted)</div>

Subject classification (UKÄ)

  • Clinical Medicine

Free keywords

  • Medicin (människa och djur)
  • Medicine (human and vertebrates)
  • basic helix-loop-helix
  • Neuroblastoma
  • Breast cancer

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