Over-expression of transforming growth factor α antagonizes the anti-tumorigenic but not the differentiation actions of retinoic acid in a human teratocarcinoma cell Journal Article
| Authors: | Baselga, J.; Maerz, W. J.; Moy, D.; Miller, W. H. Jr; Castro, L.; Reuter, V. E.; Yao, T. J.; Masui, H.; Dmitrovsky, E. |
| Article Title: | Over-expression of transforming growth factor α antagonizes the anti-tumorigenic but not the differentiation actions of retinoic acid in a human teratocarcinoma cell |
| Abstract: | All-trans retinoic acid (RA) treatment of the multipotent human teratocarcinoma (TC) cell line NTERA-2 clone D1 (abbreviated NT2/D1) induces a neuronal phenotype and other cell lineages. NT2/D1 cells basally express transforming growth factor α (TGF-α) mRNA and secreted protein. After RA-treatment TGF-α expression is markedly reduced. This decline in TGF-α expression accompanies the induction of the neuronal phenotype and a marked reduction of tumorigenicity in athymic mice. This suggested a causal link between reduced TGF-α expression and the induced differentiation or loss of tumorigenicity of these RA-treated TC cells. To evaluate this possibility, an RA-refractory NT2/D1 subclone was analysed. This subclone, designated NT2/D1-R1, failed to induce differentiation or to decrease TGF-α expression despite RA treatment. To further explore the relationship between TGF-α expression and RA actions in this human TC cell, a TGF-α cDNA was stably transfected and expressed in NT2/D1 cells. RA-treatment of independently obtained TGF-α over-expressing clones and a representative control transfectant only expressing the neomycin resistance gene produced a neuronal phenotype similar to parental NT2/D1 cells as assessed by morphologic, immunophenotypic, and gene expression markers of differentiation. RA-treatment of these clones also induced a G1 arrest similar to parental cells. However, only the TGF-α over-expressing clones that secreted high levels of TGF-α protein into the conditioned media before and after RA treatment still developed tumors in athymic mice despite prior exposure of these cells to RA. This finding demonstrates that TGF-α can inhibit the anti-tumorigenic effects of RA in human TCs. Thus, over-expression of a single growth factor that normally declines with RA treatment antagonizes the antitumorigenic but not the differentiation actions of RA in this human tumor cell. |
| Keywords: | controlled study; nonhuman; flow cytometry; animal cell; phenotype; animal; mice; gene expression; cell line; animal experiment; animal model; cell differentiation; tumor cells, cultured; transfection; cell transformation, neoplastic; molecular cloning; gene expression regulation, neoplastic; nude mouse; mice, nude; rna, messenger; carcinogenicity; dna, neoplasm; transplantation, heterologous; immunophenotyping; blotting, northern; retinoic acid; g1 phase; genetic marker; carcinoma cell; transforming growth factor alpha; culture media, conditioned; tretinoin; teratocarcinoma; human; male; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
| Journal Title: | Oncogene |
| Volume: | 8 |
| Issue: | 12 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1993-12-01 |
| Start Page: | 3257 |
| End Page: | 3263 |
| Language: | English |
| PUBMED: | 8247529 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |
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