title: Identification of potential anticancer drug targets through the selection of growth-inhibitory genetic suppressor elements.
abstract: To identify human genes required for tumor cell growth, transcriptome-scale selection was used to isolate genetic suppressor elements (GSEs) inhibiting breast carcinoma cell growth. Growth-inhibitory GSEs (cDNA fragments that counteract their cognate gene) were selected from 57 genes, including known positive regulators of cell growth or carcinogenesis as well as genes that have not been previously implicated in cell proliferation. Many GSE-cognate genes encode transcription factors (such as STAT and AP-1) and signal transduction proteins. Monoclonal antibodies against a cell surface protein identified by GSE selection, neural cell adhesion molecule L1CAM, strongly inhibited the growth of several tumor cell lines but not of untransformed cells. Hence, selection for growth-inhibitory GSEs allows one to find potential targets for new anticancer drugs.
authors.affiliation: Department of Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Primiano
authors.forename: Mirza
authors.initials: M
authors.lastname: Baig
authors.forename: Anil
authors.initials: A
authors.lastname: Maliyekkel
authors.forename: Bey Dih
authors.initials: BD
authors.lastname: Chang
authors.forename: Stacey
authors.initials: S
authors.lastname: Fellars
authors.forename: Justin
authors.initials: J
authors.lastname: Sadhu
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Axenovich
authors.forename: Tatyana A
authors.initials: TA
authors.lastname: Holzmayer
authors.forename: Igor B
authors.initials: IB
authors.lastname: Roninson
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D002455:Cell Division; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015723:Gene Library; D016153:Genes, Suppressor; D006367:HeLa Cells; D006801:Humans; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014157:Transcription Factors