Role Of Betaglycan In Gonadal And Adrenal Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
TGF-beta and inhibin are related multifunctional growth factors which regulate a number of important cellular functions, including proliferation, differentiation, and survival. Betaglycan is a cell-surface protein that binds both inhibin and TGF-beta. Betaglycan appears to regulate the binding and availability of the TGF-betas and inhibins to their signaling receptors, and its presence on the cell surface increases the efficiency of TGF-beta and inhibin function. Deletion of the inhibin gene in ....TGF-beta and inhibin are related multifunctional growth factors which regulate a number of important cellular functions, including proliferation, differentiation, and survival. Betaglycan is a cell-surface protein that binds both inhibin and TGF-beta. Betaglycan appears to regulate the binding and availability of the TGF-betas and inhibins to their signaling receptors, and its presence on the cell surface increases the efficiency of TGF-beta and inhibin function. Deletion of the inhibin gene in mice produces tumours in the ovary, testis, and adrenal gland in 100% of the mice. In this current proposal, we will delete the betaglycan gene in the primary target tissues for inhibin (the anterior pituitary and gonads). The hypothesis we are testing is that the loss of a co-receptor for inhibin (i.e. betaglycan) results in a loss of cellular sensitivity to inhibin, thus resulting in altered growth characteristics which predispose the gonads and adrenals to cancer. We will examine these cells in culture and in living animals to determine whether our hypotheses are correct. We will also conduct a series of histological, biochemical, and biological experiments in order determine the underlying causes of any observed growth dysregulation. This work is expected to yield information relevant to the role of betaglycan in inhibin-TGFb-regulated processes in normal and cancerous growth, which may allow future design of therapies for cancer.Read moreRead less
Speech and chewing are accomplished automatically by the jaw muscles which have both the power to chew meat and even bone, and the precision to make extremely fine adjustments to the shape of the mouth that enable speech. The brain needs constant inputs from sensory receptors in and around the mouth to control these muscles. We will investigate how these sensory mechanisms automatically fine-tune the activity of the jaw muscles and the mechanisms that keep the jaw in its normal position when the ....Speech and chewing are accomplished automatically by the jaw muscles which have both the power to chew meat and even bone, and the precision to make extremely fine adjustments to the shape of the mouth that enable speech. The brain needs constant inputs from sensory receptors in and around the mouth to control these muscles. We will investigate how these sensory mechanisms automatically fine-tune the activity of the jaw muscles and the mechanisms that keep the jaw in its normal position when the subject is sitting quietly, or when the head is moving up and down during running. This normal rest position of the jaw is a vital point of reference for dentists who are making false teeth and for surgeons who are restoring damaged faces, but it is not known what mechanisms are responsible for it. Anyone who has experienced a sore tooth or sore jaw muscles will know that pain adversely affects normal chewing. A common symptom is limitation of jaw movements. We will determine how pain affects the control of jaw muscles. This is important for people with chronic facial pain from arthritis of the jaw joint or from grinding their teeth while they are asleep. Even if it is not possible to eliminate their pain, we hope to suggest approaches which will alleviate its effects. Another part of our study involves a computer model of the chewing system. Computer models enable scientists to examine the effect of various interventions such as surgery or orthodontics on a model before these are tried on humans. It is also possible to use such a virtual patient to answer important functional questions that cannot be examined in humans because the methods are unavailable, or because the procedures would be ethically unacceptable. The current version of the computer model is quite sophisticated anatomically, but lacks important information on the control systems that activate the muscles. We will collaborate with the developers of the model by providing this information.Read moreRead less