Chronic injections of beta-adrenergic agonist, agents that specifically raise intracellular cAMP levels and certain dietary changes, produce cell hypertrophy and hyperplasia in the rat parotid gland. Additionally, there is an increase in specific activity of the Golgi marker enzyme 4beta-galactosyltransferase. This change in activity is accompanied by an altered subcellular localization of this enzyme to the plasma membrane. The importance of up-regulation and surface localization became apparent in experiments in which agents that interact with this enzyme were shown to severely inhibit parotid gland cell hypertrophy and hyperplasia from taking place either in vitro or in vivo. Numerous reports have shown the alteration of cell surface Gal T'ase activity might be involved in cell adhesion, differentiation and tumorogenesis. Molecular studies on the regulation of the transferase, are crucial to understanding growth control in parotid and other tissues. Our basic understanding of salivary gland development and differentiation are guided by physiological and histological observations. My laboratory has provided new insights into the biochemical and molecular basis of acinar cell growth by having isolated a cDNA clone to 4beta-Gal T'ase. Our long-term goal is to understand the complex regulation of the Gal T'ase gene and how it mediates cell growth. The RCDA would allow me time to pursue several activities which would enhance my research development. During the course of the award, we propose to initiate collaborations with other salivary gland researchers with expertise in cell biology. One of our interests is the role Gal T'ase plays in developmental interactions with extracellular matrix and its contribution to cell migration. The RCDA would also allow me time for expanding my interactions with the faculty in the College of Dentistry. The pursuit of correlations in human pathologies of the oral cavity involving tissue hyperplasia will require close cooperation with the clinical and research faculty. These experiences would be extremely valuable and could be applied in my future studies of parotid gland growth and development.
| Hu, Y; Nakagawa, Y; Purushotham, K R et al. (1992) Functional changes in salivary glands of autoimmune disease-prone NOD mice. Am J Physiol 263:E607-14 |
