title: Hamartin expression and interaction with tuberin in tumor cell lines and primary cultures.
abstract: Tuberous sclerosis (TSC) is a neurocutaneous disorder characterized by multi-system hamartomatous lesions, and results from a mutation in TSC1, that encodes hamartin, or TSC2, that encodes tuberin. We have examined hamartin expression in a diverse range of human and rat cell lines and primary cultured cells derived from tissues that express hamartin in vivo. Strong hamartin signal was detected in every cell line of human origin examined, representing 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. Hamartin was also detected in the rat PC12 cell line, as well as purified primary cultures of rat cortical neurons, astrocytes, and oligodendroglia, with a stronger signal found in astrocytes. Using co-immunoprecipitation, we have also confirmed the physical interaction of tuberin and hamartin in a diverse range of human and rat cell types. These findings demonstrate that hamartin is widely expressed in human and rat cell lines and cultures, and demonstrate 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 investigations involving hamartin and tuberin both individually and as a complex, as well as studies to elucidate the mechanisms underlying the organ-specific pathology of TSC.
authors.affiliation: Department of Pathology and Laboratory Medicine (Section of Neuropathology), UCLA School of Medicine, Los Angeles, California, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Catania
authors.forename: M W
authors.initials: MW
authors.lastname: Johnson
authors.forename: L M
authors.initials: LM
authors.lastname: Liau
authors.forename: T J
authors.initials: TJ
authors.lastname: Kremen
authors.forename: J S
authors.initials: JS
authors.lastname: deVellis
authors.forename: H V
authors.initials: HV
authors.lastname: Vinters
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D014402:Tuberous Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D014407:Tumor Cells, Cultured / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: D011506:Proteins; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; C000624652:Tsc1 protein, rat; C000624655:Tsc2 protein, rat; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins