Identification of potential anticancer drug targets through the selection of growth-inhibitory genetic suppressor elements.
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.
Primiano
Thomas
T
Department of Molecular Genetics, University of Illinois at Chicago, Chicago, IL 60607, USA.
Baig
Mirza
M
Maliyekkel
Anil
A
Chang
Bey Dih
BD
Fellars
Stacey
S
Sadhu
Justin
J
Axenovich
Sergey A
SA
Holzmayer
Tatyana A
TA
Roninson
Igor B
IB
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
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014157:Transcription Factors