Phosphorylation of ERα and HIF-1α in breast cancer with focus on tamoxifen response and links to kinase activation
Författare
Summary, in English
We have identified biomarkers that were associated with tamoxifen response in a material of premenopausal breast tumours. One of the markers is Pak1, a serine/threonine protein kinase, of which high expression and particular nuclear localisation was associated with poor tamoxifen response. Two other biomarkers are different ER phosphorylations at serine 305 and serine 118; ERS305-P and ERS118-P, respectively. Tumours that were positive for ERS305 were associated with poor tamoxifen response while tumours with high expression of ERS-118 were associated with a good response. Furthermore, we have studied associations between the activated kinases responsible for these ER phosphorylations and tamoxifen response. Our observations led us to conclude that ERS118-P and ERS305-P are better tamoxifen predictive factors than their respective phosphorylating kinases, and possibly, using a combination of the phosphorylations might be even more valuable in predicting the response.
In addition, we have identified Pak1 as a regulator of the hypoxic response in breast cancer cells. More specifically, we have observed Pak1-mediated phosphorylation of the hypoxia inducible transcription factor 1α (HIF-1α). Silencing of Pak1 led to decreased HIF-1α levels and less transcriptional activity, suggesting that Pak1 phosphorylation stabilises HIF-1α and thereby increases HIF-1α’s ability to induce gene expression during tumour hypoxia.
Avdelning/ar
Publiceringsår
2009
Språk
Engelska
Publikation/Tidskrift/Serie
Lund University Faculty of Medicine Doctoral Dissertation Series
Volym
2009:39
Fulltext
Dokumenttyp
Doktorsavhandling
Förlag
Department of Laboratory Medicine, Lund University
Ämne
- Cancer and Oncology
- Cell and Molecular Biology
Status
Published
Forskningsgrupp
- Pathology, Malmö
- Göran Landberg´s Group
Handledare
- Göran Landberg
- Håkan Axelson
ISBN/ISSN/Övrigt
- ISSN: 1652-8220
- ISBN: 978-91-86253-26-4
Försvarsdatum
8 maj 2009
Försvarstid
09:00
Försvarsplats
Main Lecture Hall, Pathology Building, UMAS
Opponent
- Lesley-Ann Martin (Ph.D)