TY - JOUR
T1 - Identification of new tumor suppressor genes based on in vivo functional inactivation of a candidate gene
AU - Li, Jingfeng
AU - Protopopov, Alexei I.
AU - Gizatullin, Rinat Z.
AU - Kiss, Csaba
AU - Kashuba, Vladimir I.
AU - Winberg, Gösta
AU - Klein, George
AU - Zabarovsky, Eugene R.
N1 - Funding Information:
The authors are grateful to Dr. Ying Yang for the help in some experiments. Plasmids pUHD15-1 and pUHC13-3 were obtained from H. Bujard, University of Heidelberg, Germany. MMLV retroviral vector pLNCx was kindly provided by A.D. Miller, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. This work was supported by research grants from the Swedish Cancer Society, Karolinska Institute and Åke Wiberg foundation. J.L., C.K. and V.I.K. were recipients of fellowships from the Concern Foundation in Los Angeles and the Cancer Research Institute in New York.
PY - 1999/5/28
Y1 - 1999/5/28
N2 - As a step towards developing a new functional test for the identification of tumor suppressor genes, human wild type and mutant RB genes were expressed in the mouse A9 fibrosarcoma cell line under the transcriptional regulation of the tetracycline repressor using two new vectors: pLNCtTA and pETI. Following passage of the transfectants in immunodeficient SCID mice, the wild type RB gene was deleted or functionally inactivated already after the first passage in all 20 tumors tested. In contrast, a non-functional mutant RB gene was maintained in all 10 tumors studied. These results suggest that tests for the identification of tumor suppressor genes may be based on their functional inactivation in vivo, rather than on growth suppression. Copyright (C) 1999 Federation of European Biochemical Societies.
AB - As a step towards developing a new functional test for the identification of tumor suppressor genes, human wild type and mutant RB genes were expressed in the mouse A9 fibrosarcoma cell line under the transcriptional regulation of the tetracycline repressor using two new vectors: pLNCtTA and pETI. Following passage of the transfectants in immunodeficient SCID mice, the wild type RB gene was deleted or functionally inactivated already after the first passage in all 20 tumors tested. In contrast, a non-functional mutant RB gene was maintained in all 10 tumors studied. These results suggest that tests for the identification of tumor suppressor genes may be based on their functional inactivation in vivo, rather than on growth suppression. Copyright (C) 1999 Federation of European Biochemical Societies.
KW - Functional assay
KW - Gene expression regulation
KW - RB gene
KW - Tetracycline
KW - Tumor suppressor gene
UR - http://www.scopus.com/inward/record.url?scp=0033019359&partnerID=8YFLogxK
U2 - 10.1016/S0014-5793(99)00598-0
DO - 10.1016/S0014-5793(99)00598-0
M3 - Article
C2 - 10371207
AN - SCOPUS:0033019359
SN - 0014-5793
VL - 451
SP - 289
EP - 294
JO - FEBS Letters
JF - FEBS Letters
IS - 3
ER -