Why We Have Two Estrogen Receptors: The Role Of ERbeta In Folliculogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$576,053.00
Summary
The female hormone estrogen acts via receptors ERalpha and ERbeta. Little is known about the genes and proteins regulated by ERbeta. Ovarian granulosa cells and granulosa cell tumours express ERbeta. By studying the biology of normal and malignant granulosa cells we hope to understand the role that ERbeta plays in granulosa cells. These studies will identify areas for the development of new therapeutics or treatment strategies for a range of female-specific conditions including ovarian cancer.
Follicle-stimulating hormone (FSH) is vital for egg development, female fertility and health, and is widely used in assisted reproduction technology. But high levels of FSH are associated with premature infertility and menopause, and may lead to diseases like ovarian cancer. Understanding the biological pathways activated by elevated FSH may lead to new treatments for infertility and ovarian diseases (eg. cancer), as well as advancing new strategies for contraception.
Hormonal Influences In The Pathogenesis Of Ovarian Tumours
Funder
National Health and Medical Research Council
Funding Amount
$264,601.00
Summary
Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In orde ....Ovarian cancer is one of the most common malignancies affecting the female reproductive system. We have found that two types of tumour of the ovary produce a hormone called inhibin; these tumours are also known to produce the steroid hormone estrogen. In these studies we are seeking to determine the genetic changes in the tumours that cause the production of these hormones. We suspect that these genetic changes are also the same changes which contribute to the development of the cancers. In order to identify these genes we will draw on our knowledge of the genes that are important in the controlof growth and hormone secretion in normal ovarian cells. To assist this molecular analysis we will use two ovarian cell lines in culture that have many of the features of the primary tumours including inhibin secretion. We will also use new techniques to scan over 500 genes involved in tumours in general to see whether we detect any unusual or distinctive patterns in this sub-group of tumours. A genome wide scanning technique will be used to seek changes in the DNA of the tumours, inparticular loss of genetic material or amplification of regions. Identification of the genetic changes within these tumours should enable better systems of classification, enhance prognostication and provide specific targets for the development of appropriate treatment strategies.Read moreRead less
Developing New Therapeutic Targets And Identifying Biomarkers For Gestational Diabetes And Ovarian Cancer Using Extracellular Vesicles
Funder
National Health and Medical Research Council
Funding Amount
$1,431,623.00
Summary
Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes in Australia. Ovarian cancer (OVCA) is the most lethal gynaecological cancer, and an effective early diagnosis is critical with potential to improve patient survival. I expect to identify novel mechanisms associated with circulating extracellular vesicles (i.e. nanovesicles released from all living cells), and decipher their role in regulating maternal insulin sensitivity, and their association with OVCA progression.
Discovering The Cell Of Origin For Rare Ovarian Cancers
Funder
National Health and Medical Research Council
Funding Amount
$599,438.00
Summary
Ovarian cancer has many different varieties, and even though they all grow at the ovary, for some types we don't know the cell where the cancer starts. Using novel sequencing methods, this study will find the tissue of origin for two rare subtypes. This finding will help us to develop appropriate pre-clinical models that we can use to test emerging cancer therapies. Identifying the cell of origin will provide key insights into early detection or even prevention of these rare but deadly diseases.
OVARIAN CANCER METASTASIS: Unraveling The Biology Of The Plasminogen Activation Cascade
Funder
National Health and Medical Research Council
Funding Amount
$169,875.00
Summary
Ovarian cancer affects 1,200 new Australians every year. Compared to breast cancer where research education and early screening have improved mortality rates, the incidence of ovarian cancer has not improved and death rates have more than doubled since 1930. With few overt symptoms, ovarian cancer has an extremely poor prognosis - a staggering 71% of women diagnosed with ovarian cancer will die from the disease, compared to 21% for breast cancer. Any studies which increase our understanding of t ....Ovarian cancer affects 1,200 new Australians every year. Compared to breast cancer where research education and early screening have improved mortality rates, the incidence of ovarian cancer has not improved and death rates have more than doubled since 1930. With few overt symptoms, ovarian cancer has an extremely poor prognosis - a staggering 71% of women diagnosed with ovarian cancer will die from the disease, compared to 21% for breast cancer. Any studies which increase our understanding of the biology of ovarian cancer metastasis may lead to new therapies designed to control these processes - as such this would be a major inroad into our fight against this cancer. The aim of this novel research project is to unravel the role that one cell surface system (the plasminogen (Plg) activation cascade) plays in determining the ability of ovarian cancer cells to metastasise and regulate new tumour blood vessel formation. This study addresses the paradoxical observations that this cascade can simultaneously facilitate cancer metastasis whilst concomitantly stopping new blood vessel formation in tumours. Using a number of advanced molecular cell biology methods, the hypothesis we will test is that the capacity of ovarian cancer to metastasise is determined by differential processing of plasminogen subsequent to cell-surface Plg binding. This results in a delicate balance between the generation of cell surface proteases and the release of protein fragments capable of stopping tumour blood vessel growth. Our group is well-equipped to address this hypothesis since we have already shown that: (1) Plg binding and activation is required for cancer cell invasion; (2) Plg binding and activation is elevated on malignant compared to benign cancers (3) Plg unfolds after it binds to cell surfaces or recombinant receptors; and, (4) Plg is easily fragmented to products that inhibit new blood vessel formation after binding to some cancer cells.Read moreRead less