Digital public defence: Tine Norman Alver

MSc Tine Norman Alver at Institute of Clinical Medicine will be defending the thesis Investigating the role of Microphthalmia-Associated transcription Factor M in melanoma development and drug resistance for the degree of PhD (Philosophiae Doctor).

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Photo: Kristin Schanche

The public defence will be held as a video conference over Zoom.

The digital defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.

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Adjudication committee

  • First opponent: Research Director Corine Bertolotto, INSERM, France
  • Second opponent: Professor Oddbjørn Straume, Department of Clinical Science, University of Bergen
  • Third member and chair of the evaluation committee: Professor Bjørn Steen Skålhegg, Institute of Basic Medical Sciences, University of Oslo 

Chair of defence

Professor Tore Jahnsen, Institute of Basic Medical Sciences, University of Oslo

Principal supervisor

Sigurd Leinæs Bøe, Oslo University Hospital

Summary

Malignant melanoma is an aggressive cancer, and the prognosis is poor for patients with advanced disease. Currently, melanoma treatment consists of immunotherapy and therapy targeting the MAPK pathway. However, many patients do not respond, or develop treatment resistance. Identifying factors that contribute to melanoma initiation and/or drug resistance is therefore of interest. 

MITF-M is a master transcription factor that plays a dominant role in both melanocyte and melanoma biology, and elucidation of some of the aspects of the MITF-M protein signal pathways has been the subject of this thesis.

In the first thesis project, we identified MITF-M as a master regulator of vemurafenib (BRAF inhibitor)-induced drug resistance. During vemurafenib treatment of melanoma cell lines, loss of MITF-M was found to upregulate the ERBB3 receptor and its cognate ligand NRG, both having effect on sustained growth and survival.

Further, we investigated the role of MITF-M and SOX10 upon growth receptors their ligands using cell panels during development of vemurafenib-induced drug resistance. We suggest that identifying SOX10 and MITF levels prior to treatment initiation may offer a tool to overcome drug resistance or prolong combinatory treatment efficacy.

In our final project, the role of MITF in the context of MC1R status was investigated, as mutations in MC1R may contribute to increased risk for melanoma. Here, we developed a cell line model for studying the signaling networks that contributes to melanoma development in individual’s carrying predisposing mutations in the MC1R gene.

In conclusion, we have identified novel roles of MITF-M, contributing to increased understanding of melanoma progression and vemurafenib-induced drug resistance in melanoma.

Additional information

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Published June 15, 2020 2:50 PM - Last modified July 20, 2020 1:01 PM