Dysregulation of the high mobility group AT-hook 2 (HMGA2) gene in human tumours
Date Issued
2014-07-11
Author(s)
Supervisors
Abstract
The high mobility group AT-hook 2 (HMGA2) gene is expressed during embryogenesis but silenced in adult tissues. It often is reactivated for varying reasons depending on tissue type in a variety of malignant and benign tumours contributing to tumour growth. In this thesis, causes for dysregulation in various human tissues were investigated. A potential HMGA2 increase upon growth factor incubation was investigated in the epithelial prostate cancer cell line PC-3 as well as in human umbilical vein endothelial cells. The underlying mechanism for HMGA2 silencing in the prostate cancer cell line LNCaP was examined as well as effects of HMGA2 on cell viability. Furthermore, a small subset of uterine leiomyomas was tested by high-resolution array-based comparative genomic hybridisation to detect microdeletions potentially related to the breakpoints accompanying the typical translocation responsible for HMGA2 reactivation. An HMGA2 increase in PC-3 cells upon growth factor and FBS incubation was not detected, whereat it was shown in HUVECs upon growth factor incubation. HMGA2 in non-expressing LNCaP cells was found to be detectable after incubation with a demethylating agent, but not after silencing of DICER1, pointing rather to the involvement of DNA methylation than of miRNAs in HMGA2 silencing. Furthermore, HMGA2 incubation was associated with reduced cell viability. In two of the three uterine leiomyomas, small deletions that may be associated with the translocation were identified upstream of the HMGA2 locus. The results obtained herein underline the versatility of HMGA2 in regulation and function supporting the need for individual consideration for the development of potential therapeutic applications.
Subjects
HMGA2
;
dysregulation
;
prostate cancer
Institution
Type
Dissertation
Secondary publication
No
Language
English
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