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Cited by 521

The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.

Elevated Levels of Epidermal Growth Factor Receptor/c-erbB2 Heterodimers Mediate an Autocrine Growth Regulatory Pathway in Tamoxifen-Resistant MCF-7 Cells

Knowlden, Janice M., Hutcheson, Iain R., Jones, Helen E., Madden, Tracieann, Gee, Julia M. W., Harper, Maureen E., Barrow, Denise, Wakeling, Alan E., Nicholson, Robert I.·2003·Endocrinology
DOI 10.1210/en.2002-220620
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Abstract

The development of acquired resistance to antihormonal agents in breast cancer is a major therapeutic problem. We have developed a tamoxifen-resistant (TAM-R) MCF-7 breast cancer cell line to investigate the mechanisms behind this condition. Both epidermal growth factor receptor (EGFR) and c-erbB2 mRNA and protein expression were increased in TAM-R compared with wild-type MCF-7 cells, whereas comparable levels of c-erbB3 mRNA and protein were expressed in both cell lines. Under basal conditions, phosphorylated EGFR/c-erbB2, EGFR/c-erbB3 but not c-erbB2/c-erbB3 receptor heterodimers were detected in TAM-R cells in association with increased levels of phosphorylated extracellular-signal regulated kinase 1/2 (ERK1/2). Both cell lines were capable of generating a range of EGFR-specific ligands and increased expression of transforming growth factor α was observed in TAM-R cells. Treatment of TAM-R cells with ZD1839 (Iressa) or trastuzumab (Herceptin) blocked c-erbB receptor heterodimer formation and phosphorylation, reduced ERK1/2 activity, and strongly inhibited cell growth. The MAPK kinase inhibitor PD098059 specifically reduced phosphorylated ERK1/2 levels and inhibited TAM-R growth. All three agents abolished ERK1/2 activity in wild-type cells but caused only small reductions in cell proliferation. These results demonstrate that TAM-R MCF-7 cell growth is mediated by the autocrine release and action of an EGFR-specific ligand inducing preferential EGFR/c-erbB2 dimerization and downstream activation of the ERK pathway.

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Metadata

Authors
Knowlden, J. M., Hutcheson, I. R., Jones, H. E., Madden, T., Gee, J. M. W., Harper, M. E., Barrow, D., Wakeling, A. E., & Nicholson, R. I.
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2003-03-01
Volume
144
Issue
3
Pages
1032-1044
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2002-220620
OpenAlex
W2025005089
Cited by
521
References
54
FWCI
12.73
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Elevated Levels of Epidermal Growth Factor Receptor/c-erbB2 Heterodimers Mediate an Autocrine Growth Regulatory Pathway in Tamoxifen-Resistant MCF-7 Cells. https://app.cochat.ai/papers/10.1210/en.2002-220620
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Knowlden, J. M., Hutcheson, I. R., Jones, H. E., Madden, T., Gee, J. M. W., Harper, M. E., Barrow, D., Wakeling, A. E., & Nicholson, R. I. (2003). Elevated Levels of Epidermal Growth Factor Receptor/c-erbB2 Heterodimers Mediate an Autocrine Growth Regulatory Pathway in Tamoxifen-Resistant MCF-7 Cells. Endocrinology. https://doi.org/10.1210/en.2002-220620

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.