EGFR isoforms and gene regulation in human endometrial cancer cells

Lina Albitar, Gavin Pickett, Marilee Morgan, Jason A. Wilken, Nita Jane Maihle, Kimberly K. Leslie

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background: Epidermal growth factor (EGF) and its receptor (EGFR) constitute a principal growth-promoting pathway in endometrial cancer cells. Pre-clinical studies were undertaken to compare the expression of EGFR isoforms and the downstream effects of activating or blocking EGFR function in Ishikawa H cells, derived from a moderately differentiated type I endometrioid adenocarcinoma, or in Hec50co cells, derived from a poorly differentiated type II adenocarcinoma with papillary serous sub-differentiation.Results: We investigated whether EGFR mutations are present in the tyrosine kinase domain (exons 18-22) of EGFR and also whether EGFR isoforms are expressed in the Ishikawa H or Hec50co cell lines. Sequence of the EGFR tyrosine kinase domain proved to be wild type in both cell lines. While both cell lines expressed full-length EGFR (isoform A), EGFR and sEGFR (isoform D) were expressed at significantly lower levels in Hec50co cells compared to Ishikawa H cells. Analysis of gene expression following EGF vs. gefitinib treatment (a small molecule EGFR tyrosine kinase inhibitor) was performed. Early growth response 1, sphingosine kinase 2, dual specificity phosphatase 6, and glucocorticoid receptor DNA binding factor 1 are members of a cluster of genes downstream of EGFR that are differentially regulated by treatment with EGF compared to gefitinib in Ishikawa H cells, but not in Hec50co cells.Conclusions: Type I Ishikawa H and type II Hec50co endometrial carcinoma cells both express EGFR and sEGFR, but differ markedly in their responsiveness to the EGFR inhibitor gefitinib. This difference is paralleled by differences in the expression of sEGFR and EGFR, as well as in their transcriptional response following treatment with either EGF or gefitinib. The small cluster of differently regulated genes reported here in these type I vs. type II endometrial cancer-derived cell lines may identify candidate biomarkers useful for predicting sensitivity to EGFR blockade.

Original languageEnglish (US)
Article number166
JournalMolecular Cancer
Volume9
DOIs
StatePublished - Jun 25 2010

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Endometrial Neoplasms
Epidermal Growth Factor Receptor
Protein Isoforms
Genes
Epidermal Growth Factor
Protein-Tyrosine Kinases
Cell Line
Dual Specificity Phosphatase 6
Papillary Adenocarcinoma
Endometrioid Carcinoma
Glucocorticoid Receptors
Multigene Family
Growth
Exons

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

Cite this

Albitar, L., Pickett, G., Morgan, M., Wilken, J. A., Maihle, N. J., & Leslie, K. K. (2010). EGFR isoforms and gene regulation in human endometrial cancer cells. Molecular Cancer, 9, [166]. https://doi.org/10.1186/1476-4598-9-166

EGFR isoforms and gene regulation in human endometrial cancer cells. / Albitar, Lina; Pickett, Gavin; Morgan, Marilee; Wilken, Jason A.; Maihle, Nita Jane; Leslie, Kimberly K.

In: Molecular Cancer, Vol. 9, 166, 25.06.2010.

Research output: Contribution to journalArticle

Albitar, L, Pickett, G, Morgan, M, Wilken, JA, Maihle, NJ & Leslie, KK 2010, 'EGFR isoforms and gene regulation in human endometrial cancer cells', Molecular Cancer, vol. 9, 166. https://doi.org/10.1186/1476-4598-9-166
Albitar L, Pickett G, Morgan M, Wilken JA, Maihle NJ, Leslie KK. EGFR isoforms and gene regulation in human endometrial cancer cells. Molecular Cancer. 2010 Jun 25;9. 166. https://doi.org/10.1186/1476-4598-9-166
Albitar, Lina ; Pickett, Gavin ; Morgan, Marilee ; Wilken, Jason A. ; Maihle, Nita Jane ; Leslie, Kimberly K. / EGFR isoforms and gene regulation in human endometrial cancer cells. In: Molecular Cancer. 2010 ; Vol. 9.
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