EGFR isoforms and gene regulation in human endometrial cancer cells

Molecular Cancer

Research

Jason A Wilken¹  Nita J Maihle²  Gavin Pickett³  Marilee Morgan⁴  Lina Albitar⁵  Kimberly K Leslie⁶ 

[1] Department of Obstetrics, Gynecology, & Reproductive Sciences, Yale University School of Medicine, PO Box 208063, 310 Cedar St, 06520, New Haven, CT, USA;Department of Obstetrics, Gynecology, & Reproductive Sciences, Yale University School of Medicine, PO Box 208063, 310 Cedar St, 06520, New Haven, CT, USA;Departments of Pathology, and Pharmacology, Yale University School of Medicine, PO Box 208063, 310 Cedar St, 06520, New Haven, CT, USA;KUGR Microarray and Genomics Facility, University of New Mexico Health Sciences Center, 2325 Camino de Salud NE, 87131, Albuquerque, NM, USA;KUGR Microarray and Genomics Facility, University of New Mexico Health Sciences Center, 2325 Camino de Salud NE, 87131, Albuquerque, NM, USA;Mind Research Network, 1101 Yale Boulevard NE, 87106, Albuquerque, NM, USA;The Reproductive Molecular Biology Laboratory, Division of Maternal-Fetal Medicine, Departments of Obstetrics and Gynecology, Biochemistry and Molecular Biology, and Biomedical Sciences, University of New Mexico Health Sciences Center, 2211 Lomas Boulevard Northeast, MSC10 5580, 87131, Albuquerque, NM, USA;Department of Obstetrics and Gynecology, Harvard Medical School, Brigham and Women's Hospital, 75 Francis St, 02115, Boston, MA, USA;The Reproductive Molecular Biology Laboratory, Division of Maternal-Fetal Medicine, Departments of Obstetrics and Gynecology, Biochemistry and Molecular Biology, and Biomedical Sciences, University of New Mexico Health Sciences Center, 2211 Lomas Boulevard Northeast, MSC10 5580, 87131, Albuquerque, NM, USA;Department of Obstetrics and Gynecology, University of Iowa. Hospitals and Clinics, 200 Hawkins Drive, 52242, Iowa City, IA, USA;

关键词: Epidermal Growth Factor Receptor;    Epidermal Growth Factor;    Endometrial Cancer;    Gefitinib;    Epidermal Growth Factor Receptor Signaling;   

DOI  :  10.1186/1476-4598-9-166

 received in 2009-08-04, accepted in 2010-06-25,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundEpidermal 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.ResultsWe 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.ConclusionsType 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.

【 授权许可】

Unknown   
© Albitar et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.