TGF-beta receptor type III in normal and malignant liver growth: Modulation of TGF-beta activity [ 2001 - 2003 ]

Research Grant

Researchers: Dr Kaye Stenvers (Principal investigator) ,  Ashley Dunn

Brief description The transforming growth factor-beta (TGF-beta) family is a group of multifunctional growth factors which regulates a number of important cellular functions, including proliferation, differentiation, and survival. Therefore, the proper functioning of this system is critical for the normal development and maintenance of most tissues. Dysregulation of this system is implicated in many pathological conditions, including cancer. The actions of TGF-beta are mediated by three cell surface proteins, termed the type I, II and III TGF-beta receptors. The type I and II receptors are required for transmitting the TGF-beta signal to the nucleus of the cell. Existing data suggest that the type III receptor is not required in TGF-beta signaling but is required for the regulation of TGF-beta levels at the cell surface. However, the function of this receptor and its role in TGF-beta mediated regulation of cell growth and survival is poorly understood. Our earlier work indicated that the TGF-beta type III receptor is particularly important for limiting TGF-beta activity during normal liver development. The currently proposed research will examine the effects of type III receptor deficiency on liver cells in the adult mouse in order to determine whether alterations in cell growth and survival occur in the absence of this receptor. Becauses TGF-beta is a key regulator of liver growth and altered levels of TGF-beta in liver have been demonstrated to lead to liver cancer in mice, we anticipate that targeting the deletion of the type III gene to liver cells will provide a system in which to study compromised regulation of cell growth. This work is therefore expected to yield information relevant to the role of this receptor in TGF-beta regulated processes in normal and cancerous growth. Because the type III receptor appears to control the level of TGF-beta activity, this work will allow further evaluation of the potential for therapeutic uses for type III receptor-like agents.

Funding Amount $AUD 361,527.54

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant