Our laboratory research is focused on examining the molecular pathogenesis of pituitary and carcinoid tumors as models of endocrine tumor development and progression. We are studying the role of epigenetic changes in pituitary and carcinoid tumors and the importance of promoter methylation in pituitary tumor progression. We recently discovered that the LGALS3 gene is important for pituitary tumor development. Promoter methylation of LGALS3 and galectin-3 protein expression are currently being studied. We have developed an animal model with knockout of both the p27 and prolactin genes which leads to the rapid development of pituitary tumors. Increased expression in galectin-3 is present in these pituitaries, and there is temporal development of pituitary tumors, as they progress from hyperplasia to tumors. The tumors can lead to the death of the mice from compression of the brain. The mechanisms regulating tumor development are under study.

The role of epigenetic changes in intestinal carcinoid tumor prgression and metastasis are also under study. We have recently observed that methylation of the RASSF1A gene, and the beta catenin gene are important during the development of carcinoid tumor metastasis to the liver. We are working with the Mayo Clinic Cancer Center to perform laser capture microdissection and in situ hybridization.

Another major area of study in the laboratory is analysis of the role of chromogranins on tumor growth and progression. Transfection of chromogranin A gene into non-endocrine tumor inhibits tumor growth. The growth pattern of these non-endocrine tumors become more like endocrine tumors. The mechanisms of growth inhibition are being studied. The role of neuroendocrine-specific proconvertases, PC1/3 and PC2, in chromogranin A processing, and the effects of these proteolytic products on tumor growth and progression are currently being examined.