Bosch Prostate Cancer Focus Group
Lab head: Chris Murphy
Location: F13 - Anderson Stuart Building
Lab members: S Assinder (senior), Q Dong (senior), C Murphy (senior), J Reichardt (senior), D Richardson (senior)
Prostate cancer and benign prostatic hyperplasia
Primary supervisor: Stephen Assinder
Our research is focused on:
1. Endocrine regulation of cancer cell proliferation. In particular we are interested in how various hormones and cytokines affect tumourigenesis.
2. Oxytocin, the hormone of love. Our recent work has indicated that oxytocin acts at the prostate to increase de novo steroidogenesis. It has also shown that this hormone might also affect tissues important in regulating energy balance.
Project 1: Understanding the interaction between steroid hormones and the metastasis suppressor NDRG1 in prostate and breast cancer cells.
Prostate and breast cancers are the most prevalent neoplasms in men and women, respectively, and are responsible for 1000’s of deaths in Australia each year. These cancers are also influenced by steroid hormones including oestrogen, testosterone and progesterone, which can either drive or inhibit cancer progression, depending on the molecular context of the cancer cells. Importantly, these hormones can also influence the success of current chemotherapies.
The metastasis suppressor gene, NDRG1, plays an important role in the regulation of both prostate and breast cancers, with increased levels of this protein being correlated with less invasive cancer and better patient prognosis. Hence, NDRG1 is an ideal therapeutic target for the treatment of these cancers and a novel class of anti-cancer agents has recently been developed that can target this molecule. However, to date there has been no research into how NDRG1 is affected by steroid hormones in prostate and breast cancers, or how NDRG1 influences the response of cancer cells to these hormones. This is vital to assess, as our preliminary data demonstrates that NDRG1 can influence the expression of the oestrogen, androgen and progesterone receptors. This project will examine, for the first time, the effect of these vital hormones on NDRG1, and vice versa, in order to elucidate the complex mechanisms that determine how different cancers respond to hormones. This knowledge will be essential in terms of understanding breast and prostate cancer biology and will foster the development of more effective treatments for these deadly diseases.
Two projects will be available, with one focusing on prostate cancer, while the other focuses on breast cancer.
- Culture a range of different breast or prostate cancer cells as well as normal cells for comparison in the presence of different hormones.
- RT-PCR and Western blot analysis.
- Immunofluorescence and Confocal Microscopy
- siRNA studies to knock-down NDRG1
- MTT assays to examine cell proliferation
- 3D colony formation assays
This project is in collaboration with the Richardson Lab (Pathology) and will be co-supervised by Dr Dr. Zaklina Kovacevic and Prof. Des R. Richardson.
Project 2 How might the “hormone of love” mitigate obesity and type 2 diabetes?
Oxytocin is best known for its roles in maternal physiology. During childbirth this hormone is released from the mothers brain and acts on the uterus to induce and maintain contractions. Following birth oxytocin is important in stimulating the release of milk during breast-feeding. Since the description of these classical actions oxytocin has been shown to have key roles in modulating maternal behaviour as well as other social behaviours such as pair-bonding. Indeed, it is for these roles that oxytocin has been dubbed “the hormone of love” (reviewed in Tom and Assinder, 2010). More recent evidences suggest positive metabolic effects of oxytocin through improved glucose metabolism, circulating lipid profiles, and increased insulin sensitivity (reviewed in Elabd and Sabry, 2015; Altirriba et al., 2015). Hence, oxytocin is suggested to have pharmacological efficacy in treating obesity and type 2 diabetes.
In this project we will determine: 1) how oxytocin modulates adipose and adrenal secretion of hormones important to maintaining energy balance; 2) how oxytocin affects lipid metabolism in adipose tissue and the liver and; 3) whether it modulates liver glucose metabolism.
This project is in collaboration with Dr Andrew hoy.