This application outlines an individual Oral Pathology Training Program including advanced basic science development and research experience leading to a PhD degree in Molecular and Cellular Pathology, and advanced clinical science development leading to a certificate of training in the dental specialty of Oral Pathology. This program is designed to prepare the clinician-scientist for a productive academic career in Oral Pathology involving research, teaching and diagnostic oral pathology. The specific aims of the proposed research are to:

1) determine the level of expression of the H-ras and erbB oncogenes in chemical carcinogen-initiated hamster buccal pouch keratinocytes that exhibit a functional loss in one or more suppressor gene-controlled functions.

2) introduce the H-ras and erbB oncogenes into initiated hamster buccal pouch keratinocytes which have lost one or more suppressor-controlled functions to determine which combination of activated oncogenes and inactive/lost suppressor genes is necessary for the emergence of transformed phenotypes and ultimately tumorigenesis.

3) prepare somatic cell hybrids between transformed hamster buccal pouch keratinocytes overexpressing H-ras, erbB or both oncogenes and which have lost one or more suppressor genes, with normal and initiated keratinocytes that have intact suppressor genes. The objective of these experiments is to determine which defective suppressor-controlled functions when restored in hybrids is sufficient to abrogate the transforming effects of the H-ras and erbB oncogenes.

The long term goal of this research is to determine the in vivo significance of both loss of multiple suppressor gene functions and oncogene activation/over-expression in the evolution of hamster buccal pouch carcinomas and to determine which combination of these genetic alterations are necessary for the development of tumors in this model system of oral epithelial carcinogenesis.

K15DE000313

1991-09-30

1996-09-29