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Glossary 12-O-Tetradecanoylphorbol-13-acetate

chemical compound used to activate protein kinase C (PKC)

12-O-Tetradecanoylphorbol-13-acetate, commonly known as TPA, is a chemical compound used in biological research to activate protein kinase C (PKC). It is often employed in studies related to cell differentiation, proliferation, and apoptosis, making it a valuable tool for understanding various cellular processes and diseases, including cancer and skin conditions.

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research Protein kinase Cepsilon is linked to 12-O-tetradecanoylphorbol-13-acetate-induced tumor necrosis factor-alpha ectodomain shedding and the development of metastatic squamous cell carcinoma in protein kinase Cepsilon transgenic mice.

79 citations , October 2003 in “PubMed”

In this study, PKCepsilon transgenic mice showed increased TNFalpha shedding during skin tumor promotion, which may contribute to the development of metastatic squamous cell carcinoma.

12-O-Tetradecanoylphorbol-13-Acetate Induces Apoptosis in Renal Epithelial Cells Through a Growth Signal Conflict Prevented by Activated Ras

research 12-O-Tetradecanoylphorbol-13-acetate Induces Apoptosis in Renal Epithelial Cells through a Growth Signal Conflict Which Is Prevented by Activated ras1

4 citations , January 2001 in “Archives of Biochemistry and Biophysics”

This study found that TPA induces apoptosis in pig renal epithelial cells by affecting cell cycle proteins, and activated ras can prevent this process.

research Supplemental figure 2 from Effect of Combined Treatment with Ursolic Acid and Resveratrol on Skin Tumor Promotion by 12-O-Tetradecanoylphorbol-13-Acetate

April 2023

In this study, the combined treatment of ursolic acid and resveratrol was evaluated for its effects on skin tumor promotion in female FVB mice. The combination was applied topically before TPA treatment and was found to significantly inhibit TPA-induced epidermal hyperproliferation, signaling pathways, and skin inflammation more effectively than either compound alone. Key signaling pathways affected included EGFR, STAT3, and NF-κB, among others. The combination also increased tumor suppressor levels and reduced proinflammatory cytokine expression. Overall, the combined treatment resulted in a greater reduction in tumor multiplicity and size, highlighting its potential as a more effective strategy for inhibiting skin tumor promotion compared to individual treatments.

research Supplemental figure 2 from Effect of Combined Treatment with Ursolic Acid and Resveratrol on Skin Tumor Promotion by 12-O-Tetradecanoylphorbol-13-Acetate

April 2023

In this study, the combined treatment of ursolic acid and resveratrol was evaluated for its inhibitory effects on skin tumor promotion in female FVB mice. The combination was applied topically before TPA treatment and was found to significantly inhibit TPA-induced epidermal hyperproliferation, signaling pathways, and skin inflammation more effectively than either compound alone. Key signaling pathways affected included EGFR, STAT3, and NF-κB, among others. The combination also increased tumor suppressor levels and reduced proinflammatory cytokine expression. Overall, the combined treatment resulted in a greater reduction in tumor multiplicity and size, highlighting its potential as a more effective strategy for preventing skin tumor promotion compared to individual treatments.

research Induction of dark keratinocytes by 12-O-tetradecanoyl-phorbol-13-acetate and mezerein as an indicator of tumor-promoting efficiency

77 citations , January 1980 in “Carcinogenesis”

This study found that TPA was significantly more effective than mezerein in inducing dark basal keratinocytes in mouse skin, which may be important in early tumor promotion stages.

research Heterogeneity of ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin and in epidermal tumors

37 citations , January 1986 in “Carcinogenesis”

This study found that TPA treatment transiently induces high levels of ODC in mouse epidermal cells, particularly around hair follicles, with localization reduced by retinoic acid or cycloheximide pretreatment.

research Induction of ornithine decarboxylase in specific subpopulations of murine epidermal cells following multiple exposures to 12-O-tetradecanoylphorbol-13-acetate, mezerein and ethyl phenylpropriolate

26 citations , January 1992 in “Carcinogenesis”

This study suggests that chronic treatment with TPA in mouse skin selectively expands a keratinocyte subpopulation hyperinducible for ODC, which may be a key target for neoplastic transformation.

research Alterations in the expression of specific epidermal keratin markers in the hairless mouse by the topical application of the tumor promoters 2,3,7,8-tetrachlorodibenzo-p-dioxin and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate

12 citations , January 1987 in “Carcinogenesis”

This study found that a single application of TCDD on the skin of hairless mice altered epidermal differentiation, changing keratin expression patterns similarly to a known tumor promoter.

research The extent of the uptake of plasmid into the skin determines the immune responses induced by a DNA vaccine applied topically onto the skin

11 citations , January 2011 in “Journal of Pharmacy and Pharmacology”

This study found that inducing hair follicles into the anagen stage by plucking significantly enhances antibody responses in mice after topical DNA vaccine application, compared to retinoic acid or TPA treatments.

research Expression of keratins K6 and K16 in regenerating mouse epidermis is less restricted by cell replication than the expression of K1 and K10.

13 citations , July 1994 in “PubMed”

This study found that TPA treatment induced expression of keratins K6 and K16 in mouse epidermis, with K6 expressed across all cell layers and K16 only in post-mitotic cells.

research Overexpression of insulin-like growth factor-1 induces hyperplasia, dermal abnormalities, and spontaneous tumor formation in transgenic mice

147 citations , April 1997 in “Oncogene”

This study found that transgenic mice expressing IGF-1 in their skin showed significant skin changes, early hair follicle generation, and a higher propensity to develop tumors after chemical promotion, suggesting IGF-1's role in skin carcinogenesis.

research Targeted expression of spermidine/spermine N1-acetyltransferase increases susceptibility to chemically induced skin carcinogenesis

54 citations , February 2002 in “Carcinogenesis”

This study suggests that activation of polyamine catabolism in K6-SSAT transgenic mice may significantly increase skin tumor development and progression to carcinomas following chemical induction.

research Promotion of Skin Carcinogenesis by Dimethylarsinic Acid in Keratin (K6)/ODC Transgenic Mice

48 citations , June 2000 in “Japanese Journal of Cancer Research”

This study found that dimethylarsinic acid significantly accelerates skin tumor development in hair follicle-targeted K6/ODC transgenic mice.

research Interleukin-1β Is Differentially Expressed by Human Dermal Papilla Cells in Response to PKC Activation and Is a Potent Inhibitor of Human Hair Follicle Growth in Organ Culture

38 citations , March 1997 in “Journal of interferon & cytokine research”

This study suggests that IL-1β produced by dermal papilla cells, regulated by protein kinase C, may inhibit human hair follicle growth through paracrine signaling.

research Ornithine decarboxylase expression in cutaneous papillomas in SENCAR mice is associated with altered expression of keratins 1 and 10.

33 citations , March 1994 in “PubMed”

This study reported that high ornithine decarboxylase expression and decreased keratin K1 and K10 expression may serve as useful markers for early stages of tumor development in mouse skin.

research Conversion of C57Bl/6 mice from a tumor promotion-resistant to a -sensitive phenotype by enhanced ornithine decarboxylase expression

31 citations , September 1999 in “Molecular Carcinogenesis”

This study in a transgenic mouse model found that repressing overexpression of ornithine decarboxylase reduced papilloma development, indicating its role in tumor promotion sensitivity.

research Hair follicle stem cell proliferation, Akt and Wnt signaling activation in TPA-induced hair regeneration

30 citations , February 2017 in “Histochemistry and Cell Biology”

This study found that applying TPA to mice accelerated hair follicle regeneration by activating Akt and Wnt/ß-catenin signaling pathways, involving hair follicle stem cell proliferation.

research Correlation of proteolytic activities of organ cultured intact mouse skin with defined hair cycle stages

28 citations , June 1994 in “Journal of Dermatological Science”

This study found that proteolytic activities in murine skin vary with hair cycle stages, with significant collagenase activity during the early anagen phase.

research Suppression of Vitamin D Receptor and Induction of Retinoid X Receptor α Expression During Squamous Differentiation of Cultured Keratinocytes

15 citations , March 2000 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study found that vitamin D receptor expression is associated with proliferating keratinocytes, while retinoid X receptor α is linked to differentiating keratinocytes, suggesting differential targeting by vitamin D metabolites.

research Use of primary keratinocyte cultures from plucked human hairs for analysis of gap junctional intercellular communication

3 citations , January 1991 in “Toxicology in Vitro”

This study reports that hair follicle cultures are effective for gap junctional intercellular communication studies and can be used to assess the tumor-promoting activity of certain environmental chemicals.

research Regeneration of Mouse Skin Melanocyte Stem Cells In Vivo and In Vitro

1 citations , January 2018 in “Methods in molecular biology”

This research describes methods to activate melanocyte stem cells during hair follicle regeneration and to isolate melanocytes from neonatal mouse skin, with the aim of studying melanogenesis for potential clinical applications.

research The Roles of the Lrig1- and Lgr6-Positive Stem Cells in the Skin and the Functions of the Molecular Markers That Define Them

January 2014 in “eScholarship (California Digital Library)”

This dissertation reports that Lrig1 and Lgr6 mark distinct stem cell populations in mouse hair follicles, playing roles in tissue regeneration and tumor development, with Lgr6 regulating Wnt signaling and restraining epidermal lineage commitment.

research Abstract 2559: Targeting mTORC1 may provide selectivity for inhibiting proliferation of hair follicle stem/progenitor cells during tumor promotion

April 2012 in “Cancer research”

In this study, the authors found that targeting mTORC1 with rapamycin inhibited TPA-induced skin tumor promotion by affecting keratinocyte proliferation, including critical stem cell populations in the mouse epidermis.

research Mitogen‐regulated protein/proliferin mRNA induction following single applications of tumor promoters to murine skin

May 2005 in “Molecular Carcinogenesis”

This study found that mrp/plf-mRNA expression in murine skin increases in response to different tumor promoters, suggesting its potential as a short-term biomarker for chemical carcinogenesis.

research Epidermal cell proliferation and modulation of the protective potency of dexamethasone against phorbol ester-induced ornithine decarboxylase activity

1 citations , January 1989 in “Carcinogenesis”

This study found that dexamethasone treatment inhibited the inflammatory response and the induction of ornithine decarboxylase activity in mouse skin after TPA application, although the effect on ODC was weaker during the hyperplastic stage.

research Claudin Expression Modulations Reflect an Injury Response in the Murine Epidermis

9 citations , July 2007 in “Journal of Investigative Dermatology”

This study found that exposure to 12-O-tetradecanoyl-phorbol-13-acetate in mouse skin caused changes in claudin expression and localization, indicating disruption and eventual recovery of the epidermal barrier.

research Tumor Promotion in Skin: Are Active Oxygen Species Involved?

10 citations , January 1985 in “Elsevier eBooks”

Active oxygen species might be involved in skin tumor growth, but their exact role is unclear.

research Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR–Stat3/Akt pathway

6 citations , December 2023 in “Journal of Molecular Cell Biology”

In this study, Gsdma1/2/3 knockout mice showed reduced epidermal hyperplasia and inflammation when induced by PMA, which was attributed to decreased EGFR-Stat3/Akt signaling due to a decrease in related ligands.

Type I Keratin 17 Protein Is Phosphorylated on Serine 44 by p90 Ribosomal Protein S6 Kinase 1 in a Growth- and Stress-Dependent Fashion

research Type I Keratin 17 Protein Is Phosphorylated on Serine 44 by p90 Ribosomal Protein S6 Kinase 1 (RSK1) in a Growth- and Stress-dependent Fashion

30 citations , December 2011 in “Journal of biological chemistry/The Journal of biological chemistry”

This study found that serine 44 in the N-terminal head domain of keratin 17 is phosphorylated in response to various stimuli affecting skin keratinocyte growth, linking K17 up-regulation with growth and stress responses in skin epithelium.

research Data from Activator Protein-1 Activity Regulates Epithelial Tumor Cell Identity

March 2023

This study found that inhibiting AP-1 transcription factors in mice causes squamous tumors to transform into sebaceous tumors and regulates tumor cell lineage.