Hamartin expression and interaction with tuberin in tumor cell lines and primary cultures

Tuberous sclerosis (TSC) is a neurocutaneous disorder characterized by mult i-system hamartomatous lesions, and results from a mutation in TSC1, that e ncodes hamartin, or TSC2, that encodes tuberin. We have examined hamartin e xpression in a diverse range of human and rat cell lines and primary cultur ed cells derived from tissues that express hamartin in vivo. Strong hamarti n signal was detected in every cell line of human origin examined, represen ting neuronal, epithelial, lymphoid, renal, vascular smooth muscle, liver, and prostatic cells. Primary cell cultures of oligodendroglioma, meningioma , and glioblastoma multiforme origin were also found to express hamartin. H amartin was also detected in the rat PC12 cell line, as well as purified pr imary cultures of rat cortical neurons, astrocytes, and oligodendroglia, wi th a stronger signal found in astrocytes, Using coimmunoprecipitation, we h ave also confirmed the physical interaction of tuberin and hamartin in a di verse range of human and rat cell types. These findings demonstrate that ha martin is widely expressed in human and rat cell lines and cultures, and de monstrate that hamartin expression is not lost during the establishment of tumor cell lines or primary cultures. This suggests that the cell lines and cultures studied may serve as useful in vitro models for biochemical inves tigations involving hamartin and tuberin both individually and as a complex , as well as studies to elucidate the mechanisms underlying the organ-speci fic pathology of TSC. 276-283, 2001. (C) 2001 Wiley-Liss, Inc.