TY - JOUR
T1 - Identification of potential anticancer drug targets through the selection of growth-inhibitory genetic suppressor elements
AU - Primiano, Thomas
AU - Baig, Mirza
AU - Maliyekkel, Anil
AU - Chang, Bey Dih
AU - Fellars, Stacey
AU - Sadhu, Justin
AU - Axenovich, Sergey A.
AU - Holzmayer, Tatyana A.
AU - Roninson, Igor B.
N1 - Funding Information:
We thank Dr. Eugenia Broude for helpful discussions and advice on morphological analysis, Dr. Martha Stampfer for normal human mammary epithelial cell cultures, Dr. Victor Levenson for MDA-MB231 cells expressing ecotropic receptor, and Pamela Owings, Betty Lamar, Yan Lu, and Rachel Harte for help with sequencing and data analyses. Supported by a grant from PPD Discovery, Inc., and by the US National Cancer Institute grants R01 CA62099, R21 CA76908, and RO1 CA95727 (I.B.R.).
PY - 2003/7/1
Y1 - 2003/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0042349236&partnerID=8YFLogxK
U2 - 10.1016/S1535-6108(03)00169-7
DO - 10.1016/S1535-6108(03)00169-7
M3 - Article
C2 - 12892712
AN - SCOPUS:0042349236
SN - 1535-6108
VL - 4
SP - 41
EP - 53
JO - Cancer Cell
JF - Cancer Cell
IS - 1
ER -