Cooperation between retinoic acid and phorbol esters enhances human teratocarcinoma differentiation Journal Article
| Authors: | Kurie, J. M.; Brown, P.; Salk, E.; Scheinberg, D.; Birrer, M.; Deutsch, P.; Dmitrovsky, E. |
| Article Title: | Cooperation between retinoic acid and phorbol esters enhances human teratocarcinoma differentiation |
| Abstract: | This study explored cooperation between the retinoic acid (RA) and protein kinase C (PKC) pathways during differentiation of the multipotential human teratocarcinoma (TC) cell line NTERA-2 clone D1 (abbreviated NT2/D1). We report here that, compared to RA treatment alone, RA combined with the PKC stimulator 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced the regulated expression of the immunophenotypic differentiation markers SSEA-3, a globo-series carbohydrate, and the ganglio-series carbohydrate antigens GD2 and GD3. Northern analysis and transient transfection assays revealed that TPA co-treatment augmented the RA-induced expression and activation of the RA nuclear receptor-β (RAR-β), one early marker of RA response in NT2/D1 cells. This finding was extended with transient co-transfection experiments using a PKC-α expression vector which revealed that the PKC pathway can augment the activation of RAR-β by RA. These experiments establish PKC as a modulator of RAR-β expression in NT2/D1 cells. Similarly, experiments showed that RA can modulate activation of the PKC-responsive AP- 1 complex, a transcription factor rapidly activated by TPA. Northern analysis and transient transfection assays revealed that, compared to TPA treatment alone, RA and TPA augmented the expression and transcriptional activity of AP-1 in NT2/D1 cells. In contrast, transient transfection assays revealed no cooperative effect between RA and TPA in HeLa cells, indicating that this effect in NT2/D1 cells is cell type-specific. In summary, these studies show that stimulation of the PKC second messenger pathway can modulate tumor differentiation and transcriptional activation of a retinoid receptor associated with RA response. © 1993, International Society of Differentiation. All rights reserved. |
| Keywords: | controlled study; human cell; antigen expression; biological markers; metabolism; tumor differentiation; transcription factor; cell differentiation; transcription, genetic; tumor cells, cultured; drug synergism; gene expression regulation; gene activation; genetic transfection; immunophenotyping; protein kinase c; retinoic acid; clone cells; carbohydrate antigen; cooperation; rna transcription; phorbol ester; differentiation antigen; northern blotting; phorbol 13 acetate 12 myristate; tetradecanoylphorbol acetate; tretinoin; receptors, retinoic acid; trans-activation (genetics); teratocarcinoma; proto-oncogene proteins c-jun; human; priority journal; article; staphylococcus phage 3a; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; retinoic acid binding protein |
| Journal Title: | Differentiation |
| Volume: | 54 |
| Issue: | 2 |
| ISSN: | 0301-4681 |
| Publisher: | International Society of Differentiation |
| Date Published: | 1993-09-01 |
| Start Page: | 115 |
| End Page: | 122 |
| Language: | English |
| DOI: | 10.1111/j.1432-0436.1993.tb00714.x |
| PUBMED: | 8243888 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Source: Scopus |
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