Inhibition of stimulus-dependent epidermal growth factor receptor and transforming growth factor-α mRNA accumulation by the protein kinase C inhibitor staurosporine

Jeffrey D. Bjorge; Jeffrey E. Kudlow; Gordon B. Mills; Andrew J. Paterson

doi:10.1016/0014-5793(89)80171-1

Inhibition of stimulus-dependent epidermal growth factor receptor and transforming growth factor-α mRNA accumulation by the protein kinase C inhibitor staurosporine

Jeffrey D. Bjorge
, Jeffrey E. Kudlow
, Gordon B. Mills
, Andrew J. Paterson

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

13 Scopus citations

Abstract

The ability of staurosporine, a potent inhibitor of protein kinase C, to block certain cellular events initiated by 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) was examined. Treatment of MDA468 breast cancer cells with TPA decreases EGF binding to the cell surface and this effect is blocked by pretreatment with staurosporine with an IC₅₀ of 30 nM. Either 10^-9 M EGF or 100 ng/ml TPA stimulated the accumulation of both EGF receptor and TGF-α mRNA and staurosporine (50 nM) completely abolished these mRNA accumulations. Staurosporine did not block EGF-stimulated tyrosine phosphorylation of its receptor as measured by immunoblotting with anti-phos-photyrosine antibodies. The ability of staurosporine to block the mRNA responses of either EGF or TPA suggests that these two agents have common signaling pathways and it implies a role for protein kinase C in the control of EGF receptor and TGF-α expression.

Original language	English (US)
Pages (from-to)	404-408
Number of pages	5
Journal	FEBS Letters
Volume	243
Issue number	2
DOIs	https://doi.org/10.1016/0014-5793(89)80171-1
State	Published - Jan 30 1989
Externally published	Yes

Funding

Acknowledgements: This work was supported by grants from the National Cancer Institute (Canada) and Medical Research Council of Canada. We thank G.N. Gill for the EGF receptor probe and R. Derynck for the TGF-t~ probe.

Funders
National Institute of Health-National Cancer Institute
Medical Research Council Canada

Keywords

Growth factor receptor
Phorbol ester
Protein kinase C
Tumor promotor

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/0014-5793(89)80171-1

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title = "Inhibition of stimulus-dependent epidermal growth factor receptor and transforming growth factor-α mRNA accumulation by the protein kinase C inhibitor staurosporine",

abstract = "The ability of staurosporine, a potent inhibitor of protein kinase C, to block certain cellular events initiated by 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) was examined. Treatment of MDA468 breast cancer cells with TPA decreases EGF binding to the cell surface and this effect is blocked by pretreatment with staurosporine with an IC50 of 30 nM. Either 10-9 M EGF or 100 ng/ml TPA stimulated the accumulation of both EGF receptor and TGF-α mRNA and staurosporine (50 nM) completely abolished these mRNA accumulations. Staurosporine did not block EGF-stimulated tyrosine phosphorylation of its receptor as measured by immunoblotting with anti-phos-photyrosine antibodies. The ability of staurosporine to block the mRNA responses of either EGF or TPA suggests that these two agents have common signaling pathways and it implies a role for protein kinase C in the control of EGF receptor and TGF-α expression.",

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author = "Bjorge, \{Jeffrey D.\} and Kudlow, \{Jeffrey E.\} and Mills, \{Gordon B.\} and Paterson, \{Andrew J.\}",

note = "Funding Information: Acknowledgements: This work was supported by grants from the National Cancer Institute (Canada) and Medical Research Council of Canada. We thank G.N. Gill for the EGF receptor probe and R. Derynck for the TGF-t\textasciitilde{} probe.",

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doi = "10.1016/0014-5793(89)80171-1",

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AU - Kudlow, Jeffrey E.

AU - Mills, Gordon B.

AU - Paterson, Andrew J.

N1 - Funding Information: Acknowledgements: This work was supported by grants from the National Cancer Institute (Canada) and Medical Research Council of Canada. We thank G.N. Gill for the EGF receptor probe and R. Derynck for the TGF-t~ probe.

PY - 1989/1/30

Y1 - 1989/1/30

N2 - The ability of staurosporine, a potent inhibitor of protein kinase C, to block certain cellular events initiated by 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) was examined. Treatment of MDA468 breast cancer cells with TPA decreases EGF binding to the cell surface and this effect is blocked by pretreatment with staurosporine with an IC50 of 30 nM. Either 10-9 M EGF or 100 ng/ml TPA stimulated the accumulation of both EGF receptor and TGF-α mRNA and staurosporine (50 nM) completely abolished these mRNA accumulations. Staurosporine did not block EGF-stimulated tyrosine phosphorylation of its receptor as measured by immunoblotting with anti-phos-photyrosine antibodies. The ability of staurosporine to block the mRNA responses of either EGF or TPA suggests that these two agents have common signaling pathways and it implies a role for protein kinase C in the control of EGF receptor and TGF-α expression.

AB - The ability of staurosporine, a potent inhibitor of protein kinase C, to block certain cellular events initiated by 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) was examined. Treatment of MDA468 breast cancer cells with TPA decreases EGF binding to the cell surface and this effect is blocked by pretreatment with staurosporine with an IC50 of 30 nM. Either 10-9 M EGF or 100 ng/ml TPA stimulated the accumulation of both EGF receptor and TGF-α mRNA and staurosporine (50 nM) completely abolished these mRNA accumulations. Staurosporine did not block EGF-stimulated tyrosine phosphorylation of its receptor as measured by immunoblotting with anti-phos-photyrosine antibodies. The ability of staurosporine to block the mRNA responses of either EGF or TPA suggests that these two agents have common signaling pathways and it implies a role for protein kinase C in the control of EGF receptor and TGF-α expression.

KW - Growth factor receptor

KW - Phorbol ester

KW - Protein kinase C

KW - Tumor promotor

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Inhibition of stimulus-dependent epidermal growth factor receptor and transforming growth factor-α mRNA accumulation by the protein kinase C inhibitor staurosporine

Abstract

Funding

Keywords

ASJC Scopus subject areas

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