The pleiotropic effect of TPA on in vitro invasion/migration of glioma and melanoma cell lines

Szaniawska, B; Maternicka, Katarzyna; Kowalczyk, Dariusz W.; Miłoszewska, Joanna; Janík, P.

doi:10.1016/0304-3835(96)04369-8

Cited by 6 publications

(5 citation statements)

References 13 publications

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“…Divergent responses in different biological systems to phorbol ester-induced translocation and down-regulation have been extensively documented in the literature for the PKC isoforms. For example, although TPA causes PKC␣ and PKC␤I down-regulation in glioma cells, the same treatment of melanoma cells does not lead to changes in the levels of PKC (41). Therefore, the possibility remains that, as with PKC, the differences in RasGRP1 down-regulation in response to phorbol esters may be the result of the different cell types examined.…”

Section: Fig 6 Activation Of Erk In Mouse Keratinocytes Overexpressmentioning

confidence: 82%

RasGRP1 Represents a Novel Non-protein Kinase C Phorbol Ester Signaling Pathway in Mouse Epidermal Keratinocytes

Rambaratsingh

Stone

Blumberg

et al. 2003

Journal of Biological Chemistry

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The mouse skin model of carcinogenesis has been instrumental in our appreciation of the multistage nature of carcinogenesis. In this system, tumor promotion is a critical step in the generation of tumors and is usually achieved by treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Although it is generally assumed that protein kinase C (PKC) is the sole receptor for TPA in this system, we sought to evaluate whether non-PKC pathways could also contribute to the effects of phorbol esters in skin. We documented expression of the high affinity non-PKC phorbol ester receptor and Ras activator RasGRP1 in mouse primary keratinocytes. Overexpression of Ras-GRP1 in keratinocytes increased the level of active GTP-loaded Ras. TPA treatment further elevated this Ras activation in a PKC-independent manner and induced the translocation and down-regulation of Ras-GRP1. Overexpression of RasGRP1 in keratinocytes also caused apoptosis. Finally, induction of keratinocyte differentiation by elevation of extracellular calcium suppressed expression of endogenous RasGRP1, whereas overexpression of RasGRP1 inhibited expression of the differentiation markers keratins 1 and 10 induced by high calcium in the medium. Taken together, our results demonstrate that RasGRP1 is an additional diacylglycerol/phorbol ester receptor in epidermal keratinocytes and suggest that activation of this novel receptor may contribute to some of the phorbol ester-and Ras-mediated effects in mouse epidermis.

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Section: Fig 6 Activation Of Erk In Mouse Keratinocytes Overexpressmentioning

confidence: 82%

RasGRP1 Represents a Novel Non-protein Kinase C Phorbol Ester Signaling Pathway in Mouse Epidermal Keratinocytes

Rambaratsingh

Stone

Blumberg

et al. 2003

Journal of Biological Chemistry

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“…TPA, an activator of the protein kinase C, is known to be involved in cell proliferation, differentiation, and migration [41]. Prolonged treatment with TPA had been shown to increase migration and invasion in tumor cells [42]. SB, a histone deacetylase inhibitor, is known to inhibit proliferation, induce apoptosis and differentiation in cancer cells [43].…”

Section: Discussionmentioning

confidence: 99%

The Synergistic Effect of Chemical Carcinogens Enhances Epstein-Barr Virus Reactivation and Tumor Progression of Nasopharyngeal Carcinoma Cells

Fang

Huang

et al. 2012

PLoS ONE

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Seroepidemiological studies imply a correlation between Epstein-Barr virus (EBV) reactivation and the development of nasopharyngeal carcinoma (NPC). N-nitroso compounds, phorbols, and butyrates are chemicals found in food and herb samples collected from NPC high-risk areas. These chemicals have been reported to be risk factors contributing to the development of NPC, however, the underlying mechanism is not fully understood. We have demonstrated previously that low dose N-methyl-N’-nitro-N-nitrosoguanidine (MNNG, 0.1 µg/ml) had a synergistic effect with 12-O-tetradecanoylphorbol-13-acetate (TPA) and sodium butyrate (SB) in enhancing EBV reactivation and genome instability in NPC cells harboring EBV. Considering that residents in NPC high-risk areas may contact regularly with these chemical carcinogens, it is vital to elucidate the relation between chemicals and EBV and their contributions to the carcinogenesis of NPC. In this study, we constructed a cell culture model to show that genome instability, alterations of cancer hallmark gene expression, and tumorigenicity were increased after recurrent EBV reactivation in NPC cells following combined treatment of TPA/SB and MNNG. NPC cells latently infected with EBV, NA, and the corresponding EBV-negative cell, NPC-TW01, were periodically treated with MNNG, TPA/SB, or TPA/SB combined with MNNG. With chemically-induced recurrent reactivation of EBV, the degree of genome instability was significantly enhanced in NA cells treated with a combination of TPA/SB and MNNG than those treated individually. The Matrigel invasiveness, as well as the tumorigenicity in mouse, was also enhanced in NA cells after recurrent EBV reactivation. Expression profile analysis by microarray indicates that many carcinogenesis-related genes were altered after recurrent EBV reactivation, and several aberrations observed in cell lines correspond to alterations in NPC lesions. These results indicate that cooperation between chemical carcinogens can enhance the reactivation of EBV and, over recurrent reactivations, lead to alteration of cancer hallmark gene expression with resultant enhancement of tumorigenesis in NPC.

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“…One explanation for the conflict is that individual glioblastomas express unique profiles of PKC isozymes (Couldwell et al, 1990;Pollack et al, 1991;Szaniawska et al, 1996). PKC-a has been implicated in proliferation and in suppression of apoptosis (Shen and Glazer, 1998), whereas PKC-g augments anchorage-independent growth in cell culture (Mishima et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

The protein kinase C-η isoform induces proliferation in glioblastoma cell lines through an ERK/Elk-1 pathway

et al. 2006

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The pleiotropic effect of TPA on in vitro invasion/migration of glioma and melanoma cell lines

Cited by 6 publications

References 13 publications

RasGRP1 Represents a Novel Non-protein Kinase C Phorbol Ester Signaling Pathway in Mouse Epidermal Keratinocytes

RasGRP1 Represents a Novel Non-protein Kinase C Phorbol Ester Signaling Pathway in Mouse Epidermal Keratinocytes

The Synergistic Effect of Chemical Carcinogens Enhances Epstein-Barr Virus Reactivation and Tumor Progression of Nasopharyngeal Carcinoma Cells

The protein kinase C-η isoform induces proliferation in glioblastoma cell lines through an ERK/Elk-1 pathway

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