Hamartin and tuberin expression in human tissues

Tuberous sclerosis (TSC) is a bigenic autosomal dominant disease caused by mutations in one of two tumor-suppressor genes, TSC1 and TSC2, resulting in benign hamartomas and low grade neoplasms in multiple organs including bra in, heart, kidney, and skin. We report the results of an immunohistochemica l study of the expression of the TSC gene products, tuberin and hamartin, i n multiple tissues obtained at autopsy from 12 non-TSC affected patients ra nging in age from 20 weeks gestation to 8 years, and surgical specimens fro m some organs. Tuberin and hamartin are expressed and are colocalized in mo st tissues. Contrary to a previous report, immunostaining with our antisera detected hamartin in liver, small and large intestine, prostate, and teste s. We did not detect significant developmental differences in tuberin or ha martin expression in comparable tissues from patients of different ages. Al though tuberin and hamartin colocalize in most tissues and cell types, we p rovide data that hamartin is more abundantly expressed than tuberin in cell s within some tissues including the distal nephron and a population of cell s of the endocrine pancreas. These data support the hypothesis that hamarti n and tuberin interact and may function together in many tissues where they are co-expressed, but also suggest that hamartin has a discrete and specia lized function in certain cell types.