Projects / Programmes
The role of secretory phospholipases A2 in breast cancer
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| P310 |
Natural sciences and mathematics |
Proteins, enzymology |
secretory phospholipases A2, breast cancer, arachidonic acid, eicosanoids, prostaglandins, cell cultures, inhibitors, carcinogenesis, tumourigenesis, chemoprevention, biomembranes, protein engineering, RNA interference
Researchers (5)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
26231 |
PhD Borut Jerman |
Biochemistry and molecular biology |
Junior researcher |
2008 - 2011 |
26 |
| 2. |
00412 |
PhD Igor Križaj |
Biochemistry and molecular biology |
Researcher |
2008 - 2011 |
740 |
| 3. |
20213 |
PhD Toni Petan |
Biochemistry and molecular biology |
Researcher |
2008 - 2011 |
182 |
| 4. |
30887 |
PhD Anja Pucer Janež |
Pharmacy |
Junior researcher |
2009 - 2011 |
59 |
| 5. |
04570 |
PhD Jože Pungerčar |
Biochemistry and molecular biology |
Head |
2008 - 2011 |
320 |
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0106 |
Jožef Stefan Institute |
Ljubljana |
5051606000 |
91,767 |
Abstract
Breast cancer is the most common type of cancer among women in Europe, with over 270.000 new cases per year in the European Union countries, including about 1.000 cases in Slovenia. The role of secretory phospholipases A2 (sPLA2s) in cancer development and progression is a little investigated, but promising field of research. Recent studies have indicated an involvement of sPLA2s in the pathology of colorectal and prostate cancer. Previous work of our research group has shown that sPLA2s are involved in several important cellular processes through binding to specific intracellular proteins. Secretory PLA2s play a crucial role in liberating arachidonic acid (AA) from membrane phospholipids. AA is a precursor in the synthesis of the mitogenic prostaglandins, which have been associated with a number of malignancies, including breast cancer. Cyclooxygenase-2 (COX-2), which catalyses the first step of AA conversion to various prostaglandins, is an important target in cancer chemoprevention today. However, prolonged use of COX-2 specific inhibitors has been associated with some serious adverse effects. We will extend our studies on the role of sPLA2s in cancer development by focusing specifically on their role in AA mobilisation. Our hypothesis is that certain sPLA2s are involved in the release of AA in breast cancer cells. Since sPLA2s act upstream to the cyclooxygenase enzymes in the prostaglandin synthesis cascade, we believe that they are important mediators of breast cancer development and progression, and are suitable targets for alternative approaches in cancer treatment. The central aim of this study is to identify the sPLA2 isoforms that are crucially involved in AA production and to elucidate the mechanisms by which they influence tumourigenesis in mammals. The proposed study will importantly contribute to the elucidation of the role of sPLA2s in cancer, by opening the way to the development of new pharmacological agents for prevention and/or therapy of breast cancer.
Significance for science
The role of secretory phospholipases A2 (sPLA2s) in different physiological and pathophysiological processes is a topic that currently receives a lot of attention in the scientific community, especially with regard to the arachidonic acid metabolism and eicosanoid biosynthesis. However, the role of sPLA2s in breast cancer, the most common type of cancer among women in the developed world, has not been addressed to a significant extent yet. Our initial study of the role of sPLA2s in the arachidonic acid metabolism and its connection to breast cancer will presumably not only contribute to a better understanding of the cellular processes that enable breast cancer development and progression, but may also have an impact on research development in cancer in general. The results of the project represent an important contribution to our current knowledge of the mechanisms of action of sPLA2s and arachidonic acid metabolites in different physiological settings. Additionally, our study may open the way to developing new chemopreventive and/or chemotherapeutic modalities, based on inhibition of the eicosanoid biosynthetic pathway as a whole.
Significance for the country
This project was harmonized with the National Research and Development Programme 2006-2010 and with the first thematic priority of the Public Call: Genomic research and biotechnology for health, quality and safety of food, and sustainable development.
The long-term objective of our project was the development of alternative ways to prevent and treat cancer on the basis of inhibitors, or other medically important agents, which would interfere with the action of sPLA2s and/or the arachidonic acid metabolism. Pharmacologically interesting results could enable further strengthening of our collaboration with the pharmaceutical industry and improvement of the relationship between the scientific community and the economy in Slovenia. The development of new methods for prevention and/or treatment of breast cancer could have an important role in the efforts to lower the incidence and reoccurrence of this common disease, as well as lower the mortality rates of breast cancer patients, thereby positively influencing the socio-economic development of Slovenia. Namely, the incidence of breast cancer in Slovenia is about 1.000 cases per year and 400 women die every year due to the disease. According to the predictions of epidemiological studies the incidence of breast cancer in Slovenia is still expected to rise in the future.
The development and implementation of alternative strategies for prevention and treatment of breast cancer could have a significant impact on the improvement of the quality of life of breast cancer patients, which are confronted with long-term psychological and sociological problems in addition to their health concerns. Apart from that, the project already had a significant impact on the field of education and provided training of new research professionals in the field of life sciences. In the course of the proposed project young researchers (graduate students) were trained and undergraduate students were involved in the project during their work on the diploma theses. We also included in our study several foreign researchers and we would like to continue this collaboration also in the future. In addition, we believe that our work within the project already had a positive impact on the recognition and scientific reputation of Slovenia, especially through publications in international peer-reviewed journals and presentations at international scientific meetings.
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
