TY - JOUR
T1 - Stat3 as an oncogene
AU - Bromberg, Jacqueline F.
AU - Wrzeszczynska, Melissa H.
AU - Devgan, Geeta
AU - Zhao, Yanxiang
AU - Pestell, Richard G.
AU - Albanese, Chris
AU - Darnell, James E.
N1 - Funding Information:
We thank Xiaomin Chen, Raphael Clynes, and Paul Kaloudis for technical assistance and Lois Cousseau for preparation of the manuscript. We also thank Richard Jove and Gabriel Nunez for the Bcl-X L cDNA clone. This work was supported in part by R29CA70897 and RO1CA75503 to R. G. P. This work was supported by a James S. McDonnell Foundation Scholar Award to J. F. B. and National Insitututes of Health grants to J. E. D.
PY - 1999/8/6
Y1 - 1999/8/6
N2 - STATs are latent transcription factors that mediate cytokine- and growth factor-directed transcription. In many human cancers and transformed cell lines, Stat3 is persistently activated, and in cell culture, active Stat3 is either required for transformation, enhances transformation, or blocks apoptosis. We report that substitution of two cysteine residues within the C- terminal loop of the SH2 domain of Stat3 produces a molecule that dimerizes spontaneously, binds to DNA, and activates transcription. The Stat3-C molecule in immortalized fibroblasts causes cellular transformation scored by colony formation in soft agar and tumor formation in nude mice. Thus, the activated Stat3 molecule by itself can mediate cellular transformation and the experiments focus attention on the importance of constitutive Stat3 activation in human tumors.
AB - STATs are latent transcription factors that mediate cytokine- and growth factor-directed transcription. In many human cancers and transformed cell lines, Stat3 is persistently activated, and in cell culture, active Stat3 is either required for transformation, enhances transformation, or blocks apoptosis. We report that substitution of two cysteine residues within the C- terminal loop of the SH2 domain of Stat3 produces a molecule that dimerizes spontaneously, binds to DNA, and activates transcription. The Stat3-C molecule in immortalized fibroblasts causes cellular transformation scored by colony formation in soft agar and tumor formation in nude mice. Thus, the activated Stat3 molecule by itself can mediate cellular transformation and the experiments focus attention on the importance of constitutive Stat3 activation in human tumors.
UR - http://www.scopus.com/inward/record.url?scp=0033529704&partnerID=8YFLogxK
U2 - 10.1016/S0092-8674(00)81959-5
DO - 10.1016/S0092-8674(00)81959-5
M3 - Article
C2 - 10458605
AN - SCOPUS:0033529704
SN - 0092-8674
VL - 98
SP - 295
EP - 303
JO - Cell
JF - Cell
IS - 3
ER -
