Prostate Cancer

1. KAI1, a potential metastasis suppressor gene and the progression of primary prostatic carcinoma
2. Expression and role of angiotensin II receptors in prostate cancer.

Researcher(s):
A.G.Frauman, Department of Clinical Pharmacology and Therapeutics, Austin and Repatriation Medical Centre.

Title:
KAI1, a potential metastasis suppressor gene and the progression of primary prostatic carcinoma.

Aim:
Prostate cancer is a leading cause of death and illness in men due to its high incidence of spread to other organs. Our laboratory will examine whether a correlation exists between altered expression of a tumour suppressor, KAI1, and cancer aggressiveness in localised prostatic cancer.

Summary:
Our laboratory has shown elevated levels of KAI1 gene and protein in low grade primary prostatic cancers, with reduced levels in high grade prostatic cancer, suggesting that KAI1 may be responsible for restricting growth of low grade tumours, and that its loss allows for more aggressive tumour formation. This gene loss may therefore possibly allow us to anticipate which tumours are most likely to spread beyond the confines of the prostate gland.

The proposed project aims to expand our findings by examining the expression of KAI1 in primary prostate cancer sections stored at the Austin and Repatriation Medical Centre and correlating levels with patient outcome, including time to spread of the cancer.

Furthermore, we propose to examine the effects of KAI1 reintroduction into prostate cancer cells and prostate cancer animal models. This information may lead directly to improved prediction of aggressive behaviour of tumours and improved therapy of localised or spread tumours.

2.

Researcher(s):
Dr Simon Louis, Department of Clinical Pharmacology, Austin and Repatriation Medical Centre.

Title:
Expression and role of angiotensin II receptors in prostate cancer.

Aim:
We believe that by activating AT2-receptors or ATIP we will slow prostate tumour growth. Alternatively, drugs that block the AT1-receptor may also inhibit prostate tumour growth.

Summary:
Prostate cancer accounts for 23% of all new cases of cancer in men and is a leading cause of mortality. It frequently occurs in the aging veterans' population and current treatments can have a severe impact on the patient's quality of life.

Angiotensin II receptors are cell surface proteins. There are two types, AT1- and AT2-receptors. Stimulation of AT1-receptors causes the cells to divide, whereas activation of the AT2-receptor can slow cell growth and cause them to die. Recently, we identified a new protein, called ATIP, that interacts with the AT2-receptor inside the cell. This protein blocks pathways responsible for cell growth.

We will examine prostate tumour cell lines and prostate tumour tissues for the presence of ATIP, AT1- and AT2-receptors. In the prostate tissues we will identify the type of cells that contain these proteins and determine whether these cells are dividing or dying. The effect of stimulation and blockade of AT1- and AT2-receptors on prostate tumour cell growth will also be examined.