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Staurosporine induces protein kinase C agonist effects and maturation of normal and neoplastic mouse keratinocytes in vitro.
Cancer Res. 1991 Sep 01; 51(17):4677-84.CR

Abstract

Staurosporine is a potent but nonselective inhibitor of protein kinase C (PKC) and blocks responses to 12-O-tetradecanoylphorbol-13-acetate (TPA) in several cell types in vitro. In cultured primary mouse keratinocytes, however, staurosporine fails to inhibit TPA-mediated keratinocyte maturation and itself elicits responses that are similar to TPA (T. Sako et al., Cancer Res., 48: 4646-4650, 1988). After exposure to 10 nM staurosporine for 24 h, essentially all keratinocytes undergo morphological differentiation, whereas 160 nM TPA induces this response in about 50% of epidermal cells. These concentrations of staurosporine and TPA cause a 4-5-fold induction of epidermal transglutaminase activity and cornified envelopes, both markers of the terminal stage of keratinocyte differentiation. Staurosporine, but not TPA, also induces morphological and biochemical maturation in 2 neoplastic mouse keratinocyte cell lines, 308 and SP-1. The ability of staurosporine to elicit the same responses as TPA suggested that it may be functioning paradoxically as a PKC agonist in intact keratinocytes. In support of this hypothesis, staurosporine induces ornithine decarboxylase activity, inhibits 125I-labeled epidermal growth factor binding, and induces expression of c-fos mRNA. Down-regulation of PKC by pretreatment of primary keratinocytes with 60 nM bryostatin partially blocks staurosporine-mediated induction of cornified envelopes and inhibition of 125I-labeled epidermal growth factor binding, implicating PKC in these responses. The ability of staurosporine to mimic and/or enhance certain responses to TPA suggests that this agent is acting as a functional PKC agonist in cultured keratinocytes.

Authors+Show Affiliations

Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, Maryland 20892.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1678684

Citation

Dlugosz, A A., and S H. Yuspa. "Staurosporine Induces Protein Kinase C Agonist Effects and Maturation of Normal and Neoplastic Mouse Keratinocytes in Vitro." Cancer Research, vol. 51, no. 17, 1991, pp. 4677-84.
Dlugosz AA, Yuspa SH. Staurosporine induces protein kinase C agonist effects and maturation of normal and neoplastic mouse keratinocytes in vitro. Cancer Res. 1991;51(17):4677-84.
Dlugosz, A. A., & Yuspa, S. H. (1991). Staurosporine induces protein kinase C agonist effects and maturation of normal and neoplastic mouse keratinocytes in vitro. Cancer Research, 51(17), 4677-84.
Dlugosz AA, Yuspa SH. Staurosporine Induces Protein Kinase C Agonist Effects and Maturation of Normal and Neoplastic Mouse Keratinocytes in Vitro. Cancer Res. 1991 Sep 1;51(17):4677-84. PubMed PMID: 1678684.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Staurosporine induces protein kinase C agonist effects and maturation of normal and neoplastic mouse keratinocytes in vitro. AU - Dlugosz,A A, AU - Yuspa,S H, PY - 1991/9/1/pubmed PY - 1991/9/1/medline PY - 1991/9/1/entrez SP - 4677 EP - 84 JF - Cancer research JO - Cancer Res VL - 51 IS - 17 N2 - Staurosporine is a potent but nonselective inhibitor of protein kinase C (PKC) and blocks responses to 12-O-tetradecanoylphorbol-13-acetate (TPA) in several cell types in vitro. In cultured primary mouse keratinocytes, however, staurosporine fails to inhibit TPA-mediated keratinocyte maturation and itself elicits responses that are similar to TPA (T. Sako et al., Cancer Res., 48: 4646-4650, 1988). After exposure to 10 nM staurosporine for 24 h, essentially all keratinocytes undergo morphological differentiation, whereas 160 nM TPA induces this response in about 50% of epidermal cells. These concentrations of staurosporine and TPA cause a 4-5-fold induction of epidermal transglutaminase activity and cornified envelopes, both markers of the terminal stage of keratinocyte differentiation. Staurosporine, but not TPA, also induces morphological and biochemical maturation in 2 neoplastic mouse keratinocyte cell lines, 308 and SP-1. The ability of staurosporine to elicit the same responses as TPA suggested that it may be functioning paradoxically as a PKC agonist in intact keratinocytes. In support of this hypothesis, staurosporine induces ornithine decarboxylase activity, inhibits 125I-labeled epidermal growth factor binding, and induces expression of c-fos mRNA. Down-regulation of PKC by pretreatment of primary keratinocytes with 60 nM bryostatin partially blocks staurosporine-mediated induction of cornified envelopes and inhibition of 125I-labeled epidermal growth factor binding, implicating PKC in these responses. The ability of staurosporine to mimic and/or enhance certain responses to TPA suggests that this agent is acting as a functional PKC agonist in cultured keratinocytes. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/1678684/Staurosporine_induces_protein_kinase_C_agonist_effects_and_maturation_of_normal_and_neoplastic_mouse_keratinocytes_in_vitro_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=1678684 DB - PRIME DP - Unbound Medicine ER -