HER-2/neu raises SHP-2, stops IFN-γ anti-proliferation in bladder cancer

Wen Pin Su; I. Hwi Tu; Shiao Wen Hu; Hsuan Heng Yeh; Dar Bin Shieh; Tsai Yun Chen; Wu Chou Su

doi:10.1016/j.bbrc.2007.02.099

HER-2/neu raises SHP-2, stops IFN-γ anti-proliferation in bladder cancer

Wen Pin Su, I. Hwi Tu, Shiao Wen Hu, Hsuan Heng Yeh, Dar Bin Shieh, Tsai Yun Chen, Wu Chou Su

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Gene amplification or HER-2/neu protein overexpression signals a poor outcome for bladder cancer patients. We investigated the anti-proliferative effect of IFN-γ in HER-2/neu-transfected human bladder cancer cells (TCC-N5 and TCC-N10). The cells continued growing after IFN-γ stimulation but did not activate the Janus kinase (Jak)/Stat pathway. We found Jak/Stat protein phosphatase in TCC-N5 and TCC-N10 cells with upregulated Src homology 2-containing protein tyrosine phosphatase-2 (SHP-2). After the cells had been treated with AG825, a HER-2/neu-specific inhibitor, SHP-2 expression declined, and Jak2/Stat1 reactivated. Similar results were reported in a mouse bladder cancer cell line, MBT2, with constitutive HER-2/neu overexpression. Further, AG825 pretreatment restored the anti-proliferation activity of IFN-γ in TCC-N5 and TCC-N10 cells. Therefore, the suppression of IFN-γ signaling in HER-2/neu-overexpressing bladder cancer cells might be due to SHP-2 upregulation. The regulation of SHP-2 by HER-2/neu provides a new target for blocking the HER-2/neu oncogenic pathway.

Original language	English
Pages (from-to)	181-186
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	356
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2007.02.099
Publication status	Published - 2007 Apr 27

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bbrc.2007.02.099

Cite this

@article{45a1e239c06144369d6263f2cc72607e,

title = "HER-2/neu raises SHP-2, stops IFN-γ anti-proliferation in bladder cancer",

abstract = "Gene amplification or HER-2/neu protein overexpression signals a poor outcome for bladder cancer patients. We investigated the anti-proliferative effect of IFN-γ in HER-2/neu-transfected human bladder cancer cells (TCC-N5 and TCC-N10). The cells continued growing after IFN-γ stimulation but did not activate the Janus kinase (Jak)/Stat pathway. We found Jak/Stat protein phosphatase in TCC-N5 and TCC-N10 cells with upregulated Src homology 2-containing protein tyrosine phosphatase-2 (SHP-2). After the cells had been treated with AG825, a HER-2/neu-specific inhibitor, SHP-2 expression declined, and Jak2/Stat1 reactivated. Similar results were reported in a mouse bladder cancer cell line, MBT2, with constitutive HER-2/neu overexpression. Further, AG825 pretreatment restored the anti-proliferation activity of IFN-γ in TCC-N5 and TCC-N10 cells. Therefore, the suppression of IFN-γ signaling in HER-2/neu-overexpressing bladder cancer cells might be due to SHP-2 upregulation. The regulation of SHP-2 by HER-2/neu provides a new target for blocking the HER-2/neu oncogenic pathway.",

author = "Su, {Wen Pin} and Tu, {I. Hwi} and Hu, {Shiao Wen} and Yeh, {Hsuan Heng} and Shieh, {Dar Bin} and Chen, {Tsai Yun} and Su, {Wu Chou}",

note = "Funding Information: This work was supported by Grant NHRI-GT-EX89S912P from the Taiwan National Health Research Institutes, and Grant DOH94-TD-B-111-004 from the Taiwan Department of Health.",

year = "2007",

month = apr,

day = "27",

doi = "10.1016/j.bbrc.2007.02.099",

language = "English",

volume = "356",

pages = "181--186",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Academic Press Inc.",

number = "1",

}

TY - JOUR

T1 - HER-2/neu raises SHP-2, stops IFN-γ anti-proliferation in bladder cancer

AU - Su, Wen Pin

AU - Tu, I. Hwi

AU - Hu, Shiao Wen

AU - Yeh, Hsuan Heng

AU - Shieh, Dar Bin

AU - Chen, Tsai Yun

AU - Su, Wu Chou

N1 - Funding Information: This work was supported by Grant NHRI-GT-EX89S912P from the Taiwan National Health Research Institutes, and Grant DOH94-TD-B-111-004 from the Taiwan Department of Health.

PY - 2007/4/27

Y1 - 2007/4/27

N2 - Gene amplification or HER-2/neu protein overexpression signals a poor outcome for bladder cancer patients. We investigated the anti-proliferative effect of IFN-γ in HER-2/neu-transfected human bladder cancer cells (TCC-N5 and TCC-N10). The cells continued growing after IFN-γ stimulation but did not activate the Janus kinase (Jak)/Stat pathway. We found Jak/Stat protein phosphatase in TCC-N5 and TCC-N10 cells with upregulated Src homology 2-containing protein tyrosine phosphatase-2 (SHP-2). After the cells had been treated with AG825, a HER-2/neu-specific inhibitor, SHP-2 expression declined, and Jak2/Stat1 reactivated. Similar results were reported in a mouse bladder cancer cell line, MBT2, with constitutive HER-2/neu overexpression. Further, AG825 pretreatment restored the anti-proliferation activity of IFN-γ in TCC-N5 and TCC-N10 cells. Therefore, the suppression of IFN-γ signaling in HER-2/neu-overexpressing bladder cancer cells might be due to SHP-2 upregulation. The regulation of SHP-2 by HER-2/neu provides a new target for blocking the HER-2/neu oncogenic pathway.

AB - Gene amplification or HER-2/neu protein overexpression signals a poor outcome for bladder cancer patients. We investigated the anti-proliferative effect of IFN-γ in HER-2/neu-transfected human bladder cancer cells (TCC-N5 and TCC-N10). The cells continued growing after IFN-γ stimulation but did not activate the Janus kinase (Jak)/Stat pathway. We found Jak/Stat protein phosphatase in TCC-N5 and TCC-N10 cells with upregulated Src homology 2-containing protein tyrosine phosphatase-2 (SHP-2). After the cells had been treated with AG825, a HER-2/neu-specific inhibitor, SHP-2 expression declined, and Jak2/Stat1 reactivated. Similar results were reported in a mouse bladder cancer cell line, MBT2, with constitutive HER-2/neu overexpression. Further, AG825 pretreatment restored the anti-proliferation activity of IFN-γ in TCC-N5 and TCC-N10 cells. Therefore, the suppression of IFN-γ signaling in HER-2/neu-overexpressing bladder cancer cells might be due to SHP-2 upregulation. The regulation of SHP-2 by HER-2/neu provides a new target for blocking the HER-2/neu oncogenic pathway.

UR - http://www.scopus.com/inward/record.url?scp=33947267984&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947267984&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2007.02.099

DO - 10.1016/j.bbrc.2007.02.099

M3 - Article

C2 - 17346677

AN - SCOPUS:33947267984

SN - 0006-291X

VL - 356

SP - 181

EP - 186

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 1

ER -

HER-2/neu raises SHP-2, stops IFN-γ anti-proliferation in bladder cancer

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this