Cytokine expression & TGF-beta signaling in cervical cancer

Leiden Repository

Cytokine expression & TGF-beta signaling in cervical cancer

Type: Doctoral Thesis
Title: Cytokine expression & TGF-beta signaling in cervical cancer
Author: Kloth, Judith Nathalie
Publisher: Department Pathology, Faculty of Medicine / Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2009-01-28
Keywords: Cervical cancer
Cytokines
Microarray
TGFbeta
Abstract: Immune surveillance is of utmost importance in preventing cervical carcinogenesis. Cytokines play a central role in directing and fine tuning the immune response. In cancer, cytokines can either be involved in stimulating the anti-tumor immune response or in tumor growth and progression. The studies in this thesis concern molecular analyses of immune escape mechanisms besides HLA class I loss, such as loss of TNFα expression and TGF-β insensitivity in cervical cancer. We identified SerpinA1 and SerpinA3 as candidate genes involved in immune suppression and/or carcinogenesis in HLA positive tumors. With regard to TGF-β insensitivity, we showed in an in vitro model that TGF-β insensitivity in cervical cancer cells is associated with activation of pathways involved in proliferation like MAPK. Furthermore, we provide evidence that the TGF-β-Smad signaling pathway is functional in most cervical carcinomas and that inactivation of Smad2 or Smad4 genes as a cause for TGF-β insensitivity is unlikely. Overall, the studies in this thesis show that loss of HLA class I, lack of TNFα expression, resistance to TGF-β growth inhibition, production of TGF-β and SerpinA1 and/or SerpinA3 expression occur in cervical cancer cells and represent possible strategies to evade eradication by immune cells.
Description: Promotores: G.J. Fleuren, G.G. Kenter, Co-promotor: A. Gorter
With summary in Dutch
Faculty: LUMC
Citation: Kloth, J.N., 2009, Doctoral thesis, Leiden University
ISBN: 9789071382796
Sponsor: Dutch Cancer Society Stichting Nationaal Fonds tegen Kanker J.E. Jurriaanse Stichting
Handle: http://hdl.handle.net/1887/13438
 

Files in this item

Description Size View
application/pdf Full text 33.69Mb View/Open
application/pdf Cover 7.847Mb View/Open
application/pdf Title page_Contents 28.31Kb View/Open
application/pdf Chapter 1 355.4Kb View/Open
application/pdf Chapter 2 706.3Kb View/Open Full text at publisher site
application/pdf Chapter 3 433.3Kb View/Open Full text at publisher site
application/pdf Chapter 4 379.2Kb View/Open Full text at publisher site
application/pdf Chapter 5 771.1Kb View/Open Full text at publisher site
application/pdf Chapter 6 444.7Kb View/Open Full text at publisher site
application/pdf Chapter 7 134.8Kb View/Open
application/pdf Chapter 8 42.00Kb View/Open
application/pdf Curriculum vita ... ications_Acknowledgements 31.49Kb View/Open
application/pdf Colour illustrations 627.9Kb View/Open
application/pdf Propositions 11.78Kb View/Open

This item appears in the following Collection(s)