Regulation Of Innate Immunity And Tumour Progression By Activating Transcription Factor 3
Funder
National Health and Medical Research Council
Funding Amount
$473,469.00
Summary
Toll-like receptors (TLRs) play an essential role in innate immune responses and are involved in initiating tumourigenesis via inflammatory pathways. We have shown that the transcription factor ATF3 is a negative regulator of TLR signalling. We will study how modulation of the activity of ATF3 affects the inflammatory response and tumour progression. This will provide a molecular basis on which to design therapeutic reagents for the treatment of cancer.
Understanding The Role Of PI 3-kinase Mutations In Gastrointestinal Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$283,880.00
Summary
Mutations in the PIK3CA gene are frequently found in bowel cancers but it remains unclear exactly how these mutations are involved in cancer development. We will exploit a unique mouse model to explore the role of PIK3CA mutations in the initiation, progression and-or metastasis of gastrointestinal cancers. This work will provide critical new insights into the biology of PIK3CA mutations and lead to the development of better models for the testing of new anti-cancer therapies.
Identification Of Novel ERBB2 Co-operating Tumor Suppressors Using In Vivo RNAi Screens.
Funder
National Health and Medical Research Council
Summary
Invasive breast cancer is often lethal, however, noninvasive disease has a >98% survival rate. Thus, understanding how breast cancer develops invasive ability is an important research goal. Using a new method in mice predisposed to breast cancer, we will find genes that prevent tumor invasion and determine if they are important in human cancer. By understanding how these genes restrict tumor invasion, we hope to develop therapies to improve breast cancer treatment.
Studies On The Tumour-associated PIK3CA(H1047R) Mutation Using In Vitro And In Vivo Models Of Breast And Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$583,312.00
Summary
PIK3CA mutations are frequently found in breast and ovarian cancers but how they cause cancer is not clear. We will exploit a unique mouse model to investigate the functional effects of PIK3CA mutations in cells and their role in cancer development. Understanding the mechanisms by which PIK3CA mutations regulate cell function and drive tumour growth will allow the rationale design of novel anti-cancer agents that specifically target this important cancer pathway.
Identifying Modifiers For Plasmacytoma Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$265,500.00
Summary
Many oncogenes and tumour suppressor genes have been identified. Activation or deletion of these genes can have profound effects on the control of cell growth and result in tumours. Many tumour suppressor genes give carriers an elevated risk of disease. However in many cases the incidence of these mutations causing cancer is much lower than would be expected, due to other influencing factors. This project aims to try and understand the reasons behind this in a mouse model of cancer, plasmacytoma ....Many oncogenes and tumour suppressor genes have been identified. Activation or deletion of these genes can have profound effects on the control of cell growth and result in tumours. Many tumour suppressor genes give carriers an elevated risk of disease. However in many cases the incidence of these mutations causing cancer is much lower than would be expected, due to other influencing factors. This project aims to try and understand the reasons behind this in a mouse model of cancer, plasmacytomas. Modifers of tumour incidence are proposed for human disease but very little is known about the identity of the genes involved or in the biological pathways regulating tumour incidence. The search for these genes in humans is difficult. We have begun studies to find modifiers of tumourigenesis using the E -v-abl transgenic model of plasmacytomas. This is the mouse equivalent of multiple myeloma. Studies have shown that some strains of mice have markedly different incidences of tumours. C57BL-6 animals are less susceptible with 20% of animals developing tumour by 12 months of age. In contrast, 90% of transgenic animals on the BALB-c background develop tumour by 12 months of age. There is also a significant sex difference with males being more susceptible than females. There is a similar difference in susceptibility in humans to multiple myeloma.Read moreRead less