Regulation of cellular growth and identification of stromal gene signatures in breast cancer
Author
Summary, in English
G3BP2 belongs to a family of three homologous proteins with RNA-regulating capacities. With the aim to identify specific RNA targets, we performed a gene expression analysis and detected a negative regulation of the peripheral myelin protein (PMP22) by the G3BP1 isoform. The previously reported growth suppressing effects by PMP22 was here verified in breast cancer cells and we could show that G3BP1 influences growth regulation by reducing PMP22 expression, although not through mRNA destabilizing mechanisms.
Another RNA regulating mechanism that can promote or prevent tumor progression are mRNA silencing through miRNA. We analyzed miR-34c and its function in breast cancer and identified impaired cell growth, induced apoptosis and cell cycle G2/M arrest, which might be due to regulation of the anaphase-promoting complex protein Cdc23.
The tumor is not a homogenous compartment, but consists of various different cell types, both among the cancer cells as well as in the surrounding stroma. We have developed a methodological procedure for isolation and characterization of cancer- and stroma-specific genes using laser capture microdissection on FFPE triple negative breast cancers. Gene expression microarrays of these samples revealed compartment specific gene expression and enabled identification of stromal-specific gene signatures with tumor-predictive capacity.
Department/s
- Division of Translational Cancer Research
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2014
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2014:55
Full text
Document type
Dissertation
Publisher
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund
Topic
- Cancer and Oncology
Keywords
- Breast cancer
- cellular stress
- proliferation
- PKCα
- G3BP
- PMP22
- miR-34c
- gene expression profiles
- stroma
Status
Published
Supervisor
- Christer Larsson
- Anders Edsjö
- Karin Leandersson
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-87651-81-6
Defence date
15 May 2014
Defence time
09:00
Defence place
Forum conference room, Ideon Agora, Scheelevägen 15, Lund
Opponent
- Pierre Åman (Ph.D.)