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The Autocrine Loop of Epidermal Growth Factor Receptor‐Epidermal Growth Factor/Transforming Growth Factor‐α in Malignant Rhabdoid Tumor Cell Lines: Heterogeneity of Autocrine Mechanism in TTC549
To investigate the effects of the autocrine loop of epidermal growth factor receptor (EGFR)‐epidermal growth factor (EGF)/transforming growth factor‐α (TGF‐α) on the proliferation and differentiation of malignant rhabdoid tumor (MRT), we used five MRT cell lines, TM87‐16, STM91‐01, TTC549, TTC642, a...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2001
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926717/ https://www.ncbi.nlm.nih.gov/pubmed/11267936 http://dx.doi.org/10.1111/j.1349-7006.2001.tb01091.x |
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author | Narita, Tsutomu Taga, Takashi Sugita, Kanji Nakazawa, Shinpei Ohta, Shigeru |
author_facet | Narita, Tsutomu Taga, Takashi Sugita, Kanji Nakazawa, Shinpei Ohta, Shigeru |
author_sort | Narita, Tsutomu |
collection | PubMed |
description | To investigate the effects of the autocrine loop of epidermal growth factor receptor (EGFR)‐epidermal growth factor (EGF)/transforming growth factor‐α (TGF‐α) on the proliferation and differentiation of malignant rhabdoid tumor (MRT), we used five MRT cell lines, TM87‐16, STM91‐01, TTC549, TTC642, and YAM‐RTK1. RT‐PCR analyses revealed expression of EGFR mRNA in all MRT cell lines. In contrast, the expression of either EGF or TGF‐α mRNA was detected in all MRT cell lines. Expression of EGF, TGF‐α, and EGFR as determined by immunocytochemical staining and in situ hybridization, correlated with the results of RT‐PCR. Upon differentiation‐induction with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), in TTC549, showing an expression of TGF‐α but not EGF initially, de novo expression of EGF mRNA appeared abruptly on day 2 of TPA treatment. To confirm the EGFR‐EGF/TGF‐α autocrine loop, we used TGF‐α, EGF, and their antibodies in the cultures. Monoclonal antibody (mAb) to EGFR alone significantly inhibited the growth of cell line TTC549. However, mAb to EGF or TGF‐α could inhibit proliferation of this cell line only when administrated together. Our findings would suggest that growth of the TTC549 cell line is constitutionally regulated by TGF‐α/EGFR, but that inhibition of this autocrine mechanism results in transient activation of an autocrine loop involving EGF/EGFR. Our results may indicate the presence of two different autocrine loops of EGFR‐EGF and/or EGFR‐TGF‐α in MRT cell lines. The heterogeneity of autocrine mechanisms found in MRT cell lines would be consistent with the multiphenotypic diversity and aggressive characteristics of this enigmatic tumor. |
format | Online Article Text |
id | pubmed-5926717 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-59267172018-05-11 The Autocrine Loop of Epidermal Growth Factor Receptor‐Epidermal Growth Factor/Transforming Growth Factor‐α in Malignant Rhabdoid Tumor Cell Lines: Heterogeneity of Autocrine Mechanism in TTC549 Narita, Tsutomu Taga, Takashi Sugita, Kanji Nakazawa, Shinpei Ohta, Shigeru Jpn J Cancer Res Article To investigate the effects of the autocrine loop of epidermal growth factor receptor (EGFR)‐epidermal growth factor (EGF)/transforming growth factor‐α (TGF‐α) on the proliferation and differentiation of malignant rhabdoid tumor (MRT), we used five MRT cell lines, TM87‐16, STM91‐01, TTC549, TTC642, and YAM‐RTK1. RT‐PCR analyses revealed expression of EGFR mRNA in all MRT cell lines. In contrast, the expression of either EGF or TGF‐α mRNA was detected in all MRT cell lines. Expression of EGF, TGF‐α, and EGFR as determined by immunocytochemical staining and in situ hybridization, correlated with the results of RT‐PCR. Upon differentiation‐induction with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), in TTC549, showing an expression of TGF‐α but not EGF initially, de novo expression of EGF mRNA appeared abruptly on day 2 of TPA treatment. To confirm the EGFR‐EGF/TGF‐α autocrine loop, we used TGF‐α, EGF, and their antibodies in the cultures. Monoclonal antibody (mAb) to EGFR alone significantly inhibited the growth of cell line TTC549. However, mAb to EGF or TGF‐α could inhibit proliferation of this cell line only when administrated together. Our findings would suggest that growth of the TTC549 cell line is constitutionally regulated by TGF‐α/EGFR, but that inhibition of this autocrine mechanism results in transient activation of an autocrine loop involving EGF/EGFR. Our results may indicate the presence of two different autocrine loops of EGFR‐EGF and/or EGFR‐TGF‐α in MRT cell lines. The heterogeneity of autocrine mechanisms found in MRT cell lines would be consistent with the multiphenotypic diversity and aggressive characteristics of this enigmatic tumor. Blackwell Publishing Ltd 2001-03 /pmc/articles/PMC5926717/ /pubmed/11267936 http://dx.doi.org/10.1111/j.1349-7006.2001.tb01091.x Text en |
spellingShingle | Article Narita, Tsutomu Taga, Takashi Sugita, Kanji Nakazawa, Shinpei Ohta, Shigeru The Autocrine Loop of Epidermal Growth Factor Receptor‐Epidermal Growth Factor/Transforming Growth Factor‐α in Malignant Rhabdoid Tumor Cell Lines: Heterogeneity of Autocrine Mechanism in TTC549 |
title | The Autocrine Loop of Epidermal Growth Factor Receptor‐Epidermal Growth Factor/Transforming Growth Factor‐α in Malignant Rhabdoid Tumor Cell Lines: Heterogeneity of Autocrine Mechanism in TTC549 |
title_full | The Autocrine Loop of Epidermal Growth Factor Receptor‐Epidermal Growth Factor/Transforming Growth Factor‐α in Malignant Rhabdoid Tumor Cell Lines: Heterogeneity of Autocrine Mechanism in TTC549 |
title_fullStr | The Autocrine Loop of Epidermal Growth Factor Receptor‐Epidermal Growth Factor/Transforming Growth Factor‐α in Malignant Rhabdoid Tumor Cell Lines: Heterogeneity of Autocrine Mechanism in TTC549 |
title_full_unstemmed | The Autocrine Loop of Epidermal Growth Factor Receptor‐Epidermal Growth Factor/Transforming Growth Factor‐α in Malignant Rhabdoid Tumor Cell Lines: Heterogeneity of Autocrine Mechanism in TTC549 |
title_short | The Autocrine Loop of Epidermal Growth Factor Receptor‐Epidermal Growth Factor/Transforming Growth Factor‐α in Malignant Rhabdoid Tumor Cell Lines: Heterogeneity of Autocrine Mechanism in TTC549 |
title_sort | autocrine loop of epidermal growth factor receptor‐epidermal growth factor/transforming growth factor‐α in malignant rhabdoid tumor cell lines: heterogeneity of autocrine mechanism in ttc549 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926717/ https://www.ncbi.nlm.nih.gov/pubmed/11267936 http://dx.doi.org/10.1111/j.1349-7006.2001.tb01091.x |
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