Selective Increase of the α Subspecies of Protein Kinase C and Inhibition of Melanogenesis Induced by Retinoic Acid in Melanoma Cells

Oka, Masahiro; Ogita, Kouji; Saito, Naoaki; Mishima, Yutaka

doi:10.1038/jid.1993.77

Cited by 14 publications

(8 citation statements)

References 16 publications

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“…It has been suggested that a-PKC is involved in the regulation of melanogenesis (Gruber et al, 1992;Oka et al, 1993). Recently, however, Park et al (1993) have proposed that p-PKC stimulates melanogenesis by activating tyrosinase in melanocytes and melanoma cells.…”

Section: Discussionmentioning

confidence: 96%

“…Thus, the absence of either a-or p-PKC seems to be a property of malignant melanoma cells, rather than a change induced by the establishment of melanoma cell lines. We have shown previously that B16 mouse melanoma cells express a-, 6, E-, and s-PKC but not &PKC (Oka et al, 1993). It is of interest that the lack of aor p-PKC is a common property of human and mouse melanoma cells.…”

Section: Discussionmentioning

confidence: 97%

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Deletion of specific protein kinase C subspecies in human melanoma cells

et al. 1996

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It has been shown that tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), stimulates the proliferation of normal human melanocytes, whereas it inhibits the growth of human melanoma cell lines. The expression of protein kinase C (PKC) subspecies, the major intracellular receptors for TPA, was examined in normal melanocytes and the four melanoma cell lines HM3KO, MeWo, HMV-1, and G361. PKC was partially purified and then separated into subspecies by column chromatography on Mono Q and hydroxyapatite successively, and finally subjected to immunoblot analysis using antibodies specific for the PKC subspecies. Of the PKC subspecies examined, delta-, epsilon-, and zeta-PKC were detected in both normal melanocytes and the four melanoma cell lines. In contrast, both alpha-PKC and beta-PKC were expressed in normal melanocytes, whereas either alpha-PKC or beta-PKC was detected in melanoma cells. Specifically, HM3KO, MeWo, and HMV-1 cells were shown to contain alpha-PKC but not beta-PKC, while G361 cells expressed beta-PKC but not alpha-PKC. The growth of these melanoma cells was suppressed by TPA treatment, and the growth of the G361 cells lacking alpha-PKC was inhibited more efficiently than the other melanoma cell lines which lacked beta-PKC. It was further shown that beta-PKC was not detected in freshly isolated human primary or metastatic melanoma tissues. These results suggest that the expression of alpha-PKC or beta-PKC may be altered during the malignant transformation of normal melanocytes and that loss of alpha-PKC or beta-PKC may be related to the inhibitory effect of TPA on the growth of melanoma cells.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 97%

Deletion of specific protein kinase C subspecies in human melanoma cells

et al. 1996

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“…In addition, it has also been shown that PLD2 is regulated by various PKC isoforms (Colley et al, 1997;Siddiqi et al, 2000;Slaaby et al, 2000;Han et al, 2002). As it has been suggested that PKC plays an important part in di¡erentiation (Gruber et al, 1992;Oka et al, 1993;Park et al, 1993), proliferation (Brooks et al, 1993;Arita et al, 1994;Oka et al, 1995;La Porta et al, 2000), and transformation (Linnenbach et al, 1988;Yamanishi et al, 1991;Oka et al, 1996) in pigment cells, studies on the physiologic relevance of the diverse e¡ects of PKC isoforms in the regulation of PLD1 and PLD2 will contribute to an understanding of the biologic properties of pigment cells. Further studies, including identi¢cation of the downstream molecular targets of PLD activation, will provide important insights into the pathophysiologic role of PLD in pigment cells.…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase C α Associates with Phospholipase D1 and Enhances Basal Phospholipase D Activity in a Protein Phosphorylation-Independent Manner in Human Melanoma Cells

Oka

Kageshita

Ono

et al. 2003

Journal of Investigative Dermatology

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“…This is not the case. In contrast to a possible role of kinase C in up-regulating human pigmentation, studies in the mouse melanocyte model have shown that kinase C activation leads to a down-regulation of tyrosinase gene expression (Fuller et al, 1990;Oka et al, 1993;Bertolotto et al, 1998), and that lowering kinase C activity increases pigmentation (Englaro et al, 1998). Thus, whereas it is intriguing to speculate that yohimbine may somehow interfere with a phospholipase C/kinase C pathway, further work is needed to ascertain the role of kinase C in the regulation of pigmentation in human melanocytes, and to determine whether or not an alpha-1 adrenergic receptor is involved in yohimbine action.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of Tyrosinase Activity in Human Melanocyte Cell Cultures by Yohimbine

Fuller

Drake

Spaulding

et al. 2000

Journal of Investigative Dermatology

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Treatment of human melanocyte cell cultures with the alpha-2 adrenergic receptor antagonist yohimbine results in a marked down-regulation of tyrosinase activity. A 30% decrease occurs within 12 h of exposure of cells to yohimbine (100 microM), and by 48 h tyrosinase activity in treated melanocytes is less than a fifth that of control cultures. The inhibition is dose dependent and occurs in human melanocytes derived from either black or white skin types, and also in mouse melanoma cells. The yohimbine-induced decrease in tyrosinase activity is reversible, with enzyme levels returning to 90% of control values 48 h after removal of drug. Although tyrosinase activity is markedly suppressed by yohimbine, the compound has no effect on cell proliferation, cellular translation, or DNA synthesis. Treatment of melanocyte cultures with yohimbine blocks the increase in tyrosinase activity by either 3-isobutyl-1-methylxanthine, dibutyryl cAMP, or forskolin. Results of cAMP immunoassays, show that intracellular levels of the cyclic nucleotide are unaffected in cells treated with yohimbine. Tyrosinase inhibition by yohimbine does not involve a decrease in substrate availability since tyrosine uptake studies show that yohimbine has no effect on the amount of tyrosine entering the cell. Incubation of a melanosome-enriched fraction with yohimbine does not cause a lowering of tyrosinase activity, suggesting that an intact cell is required for yohimbine action. In addition, tyrosinase extracts show no reduction in activity when incubated directly with yohimbine, indicating that the drug does not act as a direct inhibitor of the enzyme. Finally, results of western immunoblotting show that yohimbine does not significantly lower the amount of tyrosinase protein in human melanocytes. These findings suggest that yohimbine acts through an as yet unidentified signaling pathway to lower the catalytic activity of pre-existing tyrosinase molecules present in melanocytes.

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Selective Increase of the α Subspecies of Protein Kinase C and Inhibition of Melanogenesis Induced by Retinoic Acid in Melanoma Cells

Cited by 14 publications

References 16 publications

Deletion of specific protein kinase C subspecies in human melanoma cells

Deletion of specific protein kinase C subspecies in human melanoma cells

Protein Kinase C α Associates with Phospholipase D1 and Enhances Basal Phospholipase D Activity in a Protein Phosphorylation-Independent Manner in Human Melanoma Cells

Downregulation of Tyrosinase Activity in Human Melanocyte Cell Cultures by Yohimbine

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