Okadaic acid inhibits pdgf-induced proliferation and decreases pdgf receptor number in C3H/10T1/2 mouse fibroblasts

Nicholas M. Dean; Lawrence J. Mordan; Kathy Tse; Susan L. Mooberry; Alton L. Boynton

doi:10.1093/carcin/12.4.665

Okadaic acid inhibits pdgf-induced proliferation and decreases pdgf receptor number in C3H/10T1/2 mouse fibroblasts

Nicholas M. Dean, Lawrence J. Mordan, Kathy Tse, Susan L. Mooberry, Alton L. Boynton

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

15 Scopus citations

Abstract

Okadaic acid is both a potent inhibitor of protein serine/threonine phosphatases and a tumor promoter in the mouse skin model. We have previously shown that at non-toxic nanomolar concentrations okadaic acid reversibly inhibits induction (promotion) by PDGF of transfonned cells by the 'complcte' and 'two-stage' protocols in the C3H/1OT1/2 mouse fibroblast transformation assay. In the present study we have demonstrated that treatment of confluent and proliferatively quiescent C3H/1OT1/2 mouse fibroblasts with low doses of okadaic acid inhibits the platelet-derived growth factor (PDGF)-induced mitogenic response. This inhibition is accompanied by a loss of PDGF binding sites, a decreased PDGF-induced phosphatidylinositol turnover and a decrease in the PDGF-induced intracellular calcium signal. The decrease in the PDGF-generated intracellular signalling pro cesses represents a mechanism by which okadaic acid inhibits PDGF-induced proliferation and the promotion of in vitro neoplastic transformation by PDGF.

Original language	English (US)
Pages (from-to)	665-670
Number of pages	6
Journal	Carcinogenesis
Volume	12
Issue number	4
DOIs	https://doi.org/10.1093/carcin/12.4.665
State	Published - Apr 1991
Externally published	Yes

ASJC Scopus subject areas

Cancer Research

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title = "Okadaic acid inhibits pdgf-induced proliferation and decreases pdgf receptor number in C3H/10T1/2 mouse fibroblasts",

abstract = "Okadaic acid is both a potent inhibitor of protein serine/threonine phosphatases and a tumor promoter in the mouse skin model. We have previously shown that at non-toxic nanomolar concentrations okadaic acid reversibly inhibits induction (promotion) by PDGF of transfonned cells by the 'complcte' and 'two-stage' protocols in the C3H/1OT1/2 mouse fibroblast transformation assay. In the present study we have demonstrated that treatment of confluent and proliferatively quiescent C3H/1OT1/2 mouse fibroblasts with low doses of okadaic acid inhibits the platelet-derived growth factor (PDGF)-induced mitogenic response. This inhibition is accompanied by a loss of PDGF binding sites, a decreased PDGF-induced phosphatidylinositol turnover and a decrease in the PDGF-induced intracellular calcium signal. The decrease in the PDGF-generated intracellular signalling pro cesses represents a mechanism by which okadaic acid inhibits PDGF-induced proliferation and the promotion of in vitro neoplastic transformation by PDGF.",

author = "Dean, {Nicholas M.} and Mordan, {Lawrence J.} and Kathy Tse and Mooberry, {Susan L.} and Boynton, {Alton L.}",

note = "Funding Information: This work was funded by grants from the National Institutes of Health, CA39745 (A.L.B.), CA42942 (A.L.B.), CA51498 (L.J.M.) and NIH/MBRS RR08125 (K.T.)",

year = "1991",

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doi = "10.1093/carcin/12.4.665",

language = "English (US)",

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AU - Dean, Nicholas M.

AU - Mordan, Lawrence J.

AU - Tse, Kathy

AU - Mooberry, Susan L.

AU - Boynton, Alton L.

N1 - Funding Information: This work was funded by grants from the National Institutes of Health, CA39745 (A.L.B.), CA42942 (A.L.B.), CA51498 (L.J.M.) and NIH/MBRS RR08125 (K.T.)

PY - 1991/4

Y1 - 1991/4

N2 - Okadaic acid is both a potent inhibitor of protein serine/threonine phosphatases and a tumor promoter in the mouse skin model. We have previously shown that at non-toxic nanomolar concentrations okadaic acid reversibly inhibits induction (promotion) by PDGF of transfonned cells by the 'complcte' and 'two-stage' protocols in the C3H/1OT1/2 mouse fibroblast transformation assay. In the present study we have demonstrated that treatment of confluent and proliferatively quiescent C3H/1OT1/2 mouse fibroblasts with low doses of okadaic acid inhibits the platelet-derived growth factor (PDGF)-induced mitogenic response. This inhibition is accompanied by a loss of PDGF binding sites, a decreased PDGF-induced phosphatidylinositol turnover and a decrease in the PDGF-induced intracellular calcium signal. The decrease in the PDGF-generated intracellular signalling pro cesses represents a mechanism by which okadaic acid inhibits PDGF-induced proliferation and the promotion of in vitro neoplastic transformation by PDGF.

AB - Okadaic acid is both a potent inhibitor of protein serine/threonine phosphatases and a tumor promoter in the mouse skin model. We have previously shown that at non-toxic nanomolar concentrations okadaic acid reversibly inhibits induction (promotion) by PDGF of transfonned cells by the 'complcte' and 'two-stage' protocols in the C3H/1OT1/2 mouse fibroblast transformation assay. In the present study we have demonstrated that treatment of confluent and proliferatively quiescent C3H/1OT1/2 mouse fibroblasts with low doses of okadaic acid inhibits the platelet-derived growth factor (PDGF)-induced mitogenic response. This inhibition is accompanied by a loss of PDGF binding sites, a decreased PDGF-induced phosphatidylinositol turnover and a decrease in the PDGF-induced intracellular calcium signal. The decrease in the PDGF-generated intracellular signalling pro cesses represents a mechanism by which okadaic acid inhibits PDGF-induced proliferation and the promotion of in vitro neoplastic transformation by PDGF.

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Okadaic acid inhibits pdgf-induced proliferation and decreases pdgf receptor number in C3H/10T1/2 mouse fibroblasts

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