title: The tuberous sclerosis genes, TSC1 and TSC2, trigger different gene expression responses.
abstract: Tuberous sclerosis (TSC) is an autosomal dominant tumor suppressor gene syndrome affecting about 1 in 6000 individuals. It is characterized by mental retardation and epilepsy. A variety of tumors characteristically occur in different organs of TSC patients. The genes, TSC1 on chromosome 9q34, encoding hamartin, and TSC2 on chromosome 16p13.3, encoding tuberin are responsible for TSC. Hamartin and tuberin form a complex providing a tentative explanation for the similar disease phenotype in TSC patients with mutations in either of these genes. Besides overlap in many features of patients with TSC1 and TSC2 mutations, data accumulated provide evidence for specific clinical differences. Here, we performed microarray analyses of the gene expression response to overexpressed TSC1 or TSC2 in HeLa cells. Out of 2400 analysed genes we found 115 genes to be up-regulated > or =2-fold upon ectopic TSC1 overexpression and 284 genes to be up-regulated > or =2-fold via TSC2. Only 34 of these genes were up-regulated by both, TSC1 and TSC2. Whereas only 7 genes were down-regulated > or =2-fold via TSC1, ectopic TSC2 triggered a > or =2-fold down-regulation of 113 genes. Only 3 of these genes were down-regulated by TSC1 and TSC2. This study provides new insights into the cellular roles of TSC proteins and promotes discussion on whether separable functions of these proteins might be associated with the clinical differences of TSC1- and TSC2-associated disease.
authors.affiliation: Medical Genetics, Department of Obstetrics and Gynecology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Margit
authors.initials: M
authors.lastname: Rosner
authors.forename: Angelika
authors.initials: A
authors.lastname: Freilinger
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
authors.forename: Markus
authors.initials: M
authors.lastname: Hengstschläger
mesh_terms: D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins