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Published in: Cancer Cell International 1/2013

Open Access 01-12-2013 | Primary research

Independent of ErbB1 gene copy number, EGF stimulates migration but is not associated with cell proliferation in non-small cell lung cancer

Authors: Camila Lauand, Paula Rezende-Teixeira, Beatriz Araújo Cortez, Evandro Luís de Oliveira Niero, Gláucia Maria Machado-Santelli

Published in: Cancer Cell International | Issue 1/2013

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Abstract

Background

Lung cancer often exhibits molecular changes, such as the overexpression of the ErbB1 gene. ErbB1 encodes epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, involved mainly in cell proliferation and survival. EGFR overexpression has been associated with more aggressive disease, poor prognosis, low survival rate and low response to therapy. ErbB1 amplification and mutation are associated with tumor development and are implicated in ineffective treatment. The aim of the present study was to investigate whether the ErbB1 copy number affects EGFR expression, cell proliferation or cell migration by comparing two different cell lines.

Methods

The copies of ErbB1 gene was evaluated by FISH. Immunofluorescence and Western blotting were performed to determine location and expression of proteins mentioned in the present study. Proliferation was studied by flow cytometry and cell migration by wound healing assay and time lapse.

Results

We investigated the activation and function of EGFR in the A549 and HK2 lung cancer cell lines, which contain 3 and 6 copies of ErbB1, respectively. The expression of EGFR was lower in the HK2 cell line. EGFR was activated after stimulation with EGF in both cell lines, but this activation did not promote differences in cellular proliferation when compared to control cells. Inhibiting EGFR with AG1478 did not modify cellular proliferation, confirming previous data. However, we observed morphological alterations, changes in microfilament organization and increased cell migration upon EGF stimulation. However, these effects did not seem to be consequence of an epithelial-mesenchymal transition.

Conclusion

EGFR expression did not appear to be associated to the ErbB1 gene copy number, and neither of these aspects appeared to affect cell proliferation. However, EGFR activation by EGF resulted in cell migration stimulation in both cell lines.
Appendix
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Literature
1.
go back to reference Jemal A, Thun MJ, Howe HL, Weir HK, Center MM, Ward E, Wu X-C, Eheman C, Anderson R, Kohler B, Edwards BK, Ries L a G: Annual report to the nation on the status of cancer, 1975–2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst. 2008, 100: 1672-1694. 10.1093/jnci/djn389.PubMedCentralCrossRefPubMed Jemal A, Thun MJ, Howe HL, Weir HK, Center MM, Ward E, Wu X-C, Eheman C, Anderson R, Kohler B, Edwards BK, Ries L a G: Annual report to the nation on the status of cancer, 1975–2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst. 2008, 100: 1672-1694. 10.1093/jnci/djn389.PubMedCentralCrossRefPubMed
2.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer Statistics , 2009 BOTH SEXES FEMALE BOTH SEXES ESTIMATED DEATHS. CA Cancer J Clin. 2009, 59: 225-249. 10.3322/caac.20006.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer Statistics , 2009 BOTH SEXES FEMALE BOTH SEXES ESTIMATED DEATHS. CA Cancer J Clin. 2009, 59: 225-249. 10.3322/caac.20006.CrossRefPubMed
3.
go back to reference Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P: Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007, 18: 581-592.CrossRefPubMed Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P: Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007, 18: 581-592.CrossRefPubMed
4.
go back to reference Maxwell DP: REVIEWS. Lancet Oncol. 2001, 2: 533-543. 10.1016/S1470-2045(01)00486-7.CrossRef Maxwell DP: REVIEWS. Lancet Oncol. 2001, 2: 533-543. 10.1016/S1470-2045(01)00486-7.CrossRef
5.
go back to reference Yang L, Parkin DM, Ferlay J, Li L, Chen Y: Estimates of Cancer Incidence in China for 2000 and Projections for 2005 Estimates of Cancer Incidence in China for 2000 and Projections for 2005. Cancer Epidemiol Biomarkers Prev. 2005, 14 (1): 243-250.PubMed Yang L, Parkin DM, Ferlay J, Li L, Chen Y: Estimates of Cancer Incidence in China for 2000 and Projections for 2005 Estimates of Cancer Incidence in China for 2000 and Projections for 2005. Cancer Epidemiol Biomarkers Prev. 2005, 14 (1): 243-250.PubMed
6.
go back to reference Sharma SV, Settleman J: ErbBs in lung cancer. Exp Cell Res. 2009, 315: 557-571. 10.1016/j.yexcr.2008.07.026.CrossRefPubMed Sharma SV, Settleman J: ErbBs in lung cancer. Exp Cell Res. 2009, 315: 557-571. 10.1016/j.yexcr.2008.07.026.CrossRefPubMed
7.
go back to reference Wang Y, Minoshima S, Shimizu N: Precise mapping of the EGF receptor gene on the human chromosome 7p12 using an improved fish technique. The Japanese Journal Of Human Genetics. 1993, 38: 399-406. 10.1007/BF01907986.CrossRefPubMed Wang Y, Minoshima S, Shimizu N: Precise mapping of the EGF receptor gene on the human chromosome 7p12 using an improved fish technique. The Japanese Journal Of Human Genetics. 1993, 38: 399-406. 10.1007/BF01907986.CrossRefPubMed
8.
go back to reference Jorissen RN, Walker F, Pouliot N, Garrett TPJ, Ward CW, Burgess AW: Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res. 2003, 284: 31-53. 10.1016/S0014-4827(02)00098-8.CrossRefPubMed Jorissen RN, Walker F, Pouliot N, Garrett TPJ, Ward CW, Burgess AW: Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res. 2003, 284: 31-53. 10.1016/S0014-4827(02)00098-8.CrossRefPubMed
9.
go back to reference Capdevila J, Elez E, Macarulla T, Ramos FJ, Ruiz-Echarri M, Tabernero J: Anti-epidermal growth factor receptor monoclonal antibodies in cancer treatment. Cancer Treat Rev. 2009, 35: 354-363. 10.1016/j.ctrv.2009.02.001.CrossRefPubMed Capdevila J, Elez E, Macarulla T, Ramos FJ, Ruiz-Echarri M, Tabernero J: Anti-epidermal growth factor receptor monoclonal antibodies in cancer treatment. Cancer Treat Rev. 2009, 35: 354-363. 10.1016/j.ctrv.2009.02.001.CrossRefPubMed
10.
go back to reference Sorkin A, Von Zastrow M: Signal transduction and endocytosis: close encounters of many kinds. Nat Rev Mol Cell Biol. 2002, 3: 600-614. 10.1038/nrm883.CrossRefPubMed Sorkin A, Von Zastrow M: Signal transduction and endocytosis: close encounters of many kinds. Nat Rev Mol Cell Biol. 2002, 3: 600-614. 10.1038/nrm883.CrossRefPubMed
11.
go back to reference Lewis TS, Shapiro PSAN: Signal transduction through MAP kinase cascades. Adv Cancer Res. 1998, 74: 49-139.CrossRefPubMed Lewis TS, Shapiro PSAN: Signal transduction through MAP kinase cascades. Adv Cancer Res. 1998, 74: 49-139.CrossRefPubMed
12.
go back to reference Osaki LH, Figueiredo PM, Alvares EP, Gama P: EGFR is involved in control of gastric cell proliferation through activation of MAPK and Src signalling pathways in early-weaned rats. Cell Prolif. 2011, 44: 174-182. 10.1111/j.1365-2184.2011.00733.x.CrossRefPubMed Osaki LH, Figueiredo PM, Alvares EP, Gama P: EGFR is involved in control of gastric cell proliferation through activation of MAPK and Src signalling pathways in early-weaned rats. Cell Prolif. 2011, 44: 174-182. 10.1111/j.1365-2184.2011.00733.x.CrossRefPubMed
14.
go back to reference Lurje G, Lenz H-J: EGFR signaling and drug discovery. Oncology. 2009, 77: 400-410. 10.1159/000279388.CrossRefPubMed Lurje G, Lenz H-J: EGFR signaling and drug discovery. Oncology. 2009, 77: 400-410. 10.1159/000279388.CrossRefPubMed
15.
go back to reference Jaramillo ML, Banville M, Collins C, Paul-Roc B, Bourget L, O’Connor-McCourt M: Differential sensitivity of A549 non-small lung carcinoma cell responses to epidermal growth factor receptor pathway inhibitors. Cancer Biol Ther. 2008, 7: 557-568. 10.4161/cbt.7.4.5533.CrossRefPubMed Jaramillo ML, Banville M, Collins C, Paul-Roc B, Bourget L, O’Connor-McCourt M: Differential sensitivity of A549 non-small lung carcinoma cell responses to epidermal growth factor receptor pathway inhibitors. Cancer Biol Ther. 2008, 7: 557-568. 10.4161/cbt.7.4.5533.CrossRefPubMed
16.
go back to reference Brabender J, Danenberg KD, Metzger R, Schneider PM, Park J, Salonga D, Ho AH, Danenberg PV: Advances in Brief Epidermal Growth Factor Receptor and HER2-neu mRNA Expression in Non-Small Cell Lung Cancer Is Correlated with. Survival. 2001, 7: 1850-1855. Brabender J, Danenberg KD, Metzger R, Schneider PM, Park J, Salonga D, Ho AH, Danenberg PV: Advances in Brief Epidermal Growth Factor Receptor and HER2-neu mRNA Expression in Non-Small Cell Lung Cancer Is Correlated with. Survival. 2001, 7: 1850-1855.
17.
go back to reference Amann J, Kalyankrishna S, Massion PP, Ohm JE, Girard L, Shigematsu H, Peyton M, Juroske D, Huang Y, Stuart Salmon J, Kim YH, Pollack JR, Yanagisawa K, Gazdar A, Minna JD, Kurie JM, Carbone DP: Aberrant epidermal growth factor receptor signaling and enhanced sensitivity to EGFR inhibitors in lung cancer. Cancer Res. 2005, 65: 226-235.PubMed Amann J, Kalyankrishna S, Massion PP, Ohm JE, Girard L, Shigematsu H, Peyton M, Juroske D, Huang Y, Stuart Salmon J, Kim YH, Pollack JR, Yanagisawa K, Gazdar A, Minna JD, Kurie JM, Carbone DP: Aberrant epidermal growth factor receptor signaling and enhanced sensitivity to EGFR inhibitors in lung cancer. Cancer Res. 2005, 65: 226-235.PubMed
18.
go back to reference Okabe T, Okamoto I, Tamura K, Terashima M, Yoshida T, Satoh T, Takada M, Fukuoka M, Nakagawa K: Differential constitutive activation of the epidermal growth factor receptor in non-small cell lung cancer cells bearing EGFR gene mutation and amplification. Cancer Res. 2007, 67: 2046-2053. 10.1158/0008-5472.CAN-06-3339.CrossRefPubMed Okabe T, Okamoto I, Tamura K, Terashima M, Yoshida T, Satoh T, Takada M, Fukuoka M, Nakagawa K: Differential constitutive activation of the epidermal growth factor receptor in non-small cell lung cancer cells bearing EGFR gene mutation and amplification. Cancer Res. 2007, 67: 2046-2053. 10.1158/0008-5472.CAN-06-3339.CrossRefPubMed
19.
go back to reference Mitsudomi T: Advances in target therapy for lung cancer. Jpn J Clin Oncol. 2010, 40: 101-106. 10.1093/jjco/hyp174.CrossRefPubMed Mitsudomi T: Advances in target therapy for lung cancer. Jpn J Clin Oncol. 2010, 40: 101-106. 10.1093/jjco/hyp174.CrossRefPubMed
20.
go back to reference Heigener DF, Reck M: Mutations in the epidermal growth factor receptor gene in non-small cell lung cancer: Impact on treatment beyond gefitinib and erlotinib. Adv Ther. 2011, 28: 126-133. 10.1007/s12325-010-0096-4.CrossRefPubMed Heigener DF, Reck M: Mutations in the epidermal growth factor receptor gene in non-small cell lung cancer: Impact on treatment beyond gefitinib and erlotinib. Adv Ther. 2011, 28: 126-133. 10.1007/s12325-010-0096-4.CrossRefPubMed
21.
go back to reference Pao W, Riely GJ, Somwar R, Zakowski MF, Kris MG, Varmus H, Miller V a, Politi K a: Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2005, 2: e73-10.1371/journal.pmed.0020073.PubMedCentralCrossRefPubMed Pao W, Riely GJ, Somwar R, Zakowski MF, Kris MG, Varmus H, Miller V a, Politi K a: Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2005, 2: e73-10.1371/journal.pmed.0020073.PubMedCentralCrossRefPubMed
22.
go back to reference Miller V a: EGFR mutations and EGFR tyrosine kinase inhibition in non-small cell lung cancer. Semin Oncol Nurs. 2008, 24: 27-33. 10.1016/j.soncn.2007.11.009.CrossRefPubMed Miller V a: EGFR mutations and EGFR tyrosine kinase inhibition in non-small cell lung cancer. Semin Oncol Nurs. 2008, 24: 27-33. 10.1016/j.soncn.2007.11.009.CrossRefPubMed
23.
go back to reference Zhu J, Zhong W, Zhang G, Li R, Zhang X, Guo A, Zhang Y, An S, Mok TS, Wu Y: Better survival with EGFR exon 19 than exon 21 mutations in gefitinib-treated non-small cell lung cancer patients is due to differential inhibition of downstream signals. Cancer Lett. 2008, 265: 307-317. 10.1016/j.canlet.2008.02.064.CrossRefPubMed Zhu J, Zhong W, Zhang G, Li R, Zhang X, Guo A, Zhang Y, An S, Mok TS, Wu Y: Better survival with EGFR exon 19 than exon 21 mutations in gefitinib-treated non-small cell lung cancer patients is due to differential inhibition of downstream signals. Cancer Lett. 2008, 265: 307-317. 10.1016/j.canlet.2008.02.064.CrossRefPubMed
24.
go back to reference Gandhi J, Zhang J, Xie Y, Soh J, Shigematsu H, Zhang W, Yamamoto H, Peyton M, Girard L, Lockwood WW, Lam WL, Varella-Garcia M, Minna JD, Gazdar AF: Alterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell lines. PLoS One. 2009, 4: e4576-10.1371/journal.pone.0004576.PubMedCentralCrossRefPubMed Gandhi J, Zhang J, Xie Y, Soh J, Shigematsu H, Zhang W, Yamamoto H, Peyton M, Girard L, Lockwood WW, Lam WL, Varella-Garcia M, Minna JD, Gazdar AF: Alterations in genes of the EGFR signaling pathway and their relationship to EGFR tyrosine kinase inhibitor sensitivity in lung cancer cell lines. PLoS One. 2009, 4: e4576-10.1371/journal.pone.0004576.PubMedCentralCrossRefPubMed
25.
go back to reference Bonaldo MF, Pestano MC, Ribeiro MC, Machado-Santelli GM, Mori LOA: Comparative characterization of a human large cell lung carcinoma cell line and the xenograft derived cell line. Cell Biol Int Rep. 1991, 15: 229-241. 10.1016/0309-1651(91)90155-C.CrossRef Bonaldo MF, Pestano MC, Ribeiro MC, Machado-Santelli GM, Mori LOA: Comparative characterization of a human large cell lung carcinoma cell line and the xenograft derived cell line. Cell Biol Int Rep. 1991, 15: 229-241. 10.1016/0309-1651(91)90155-C.CrossRef
26.
go back to reference Bustin S a: Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems. J Mol Endocrinol. 2002, 29: 23-39. 10.1677/jme.0.0290023.CrossRefPubMed Bustin S a: Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems. J Mol Endocrinol. 2002, 29: 23-39. 10.1677/jme.0.0290023.CrossRefPubMed
27.
go back to reference Bustin S a: Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol. 2000, 25: 169-193. 10.1677/jme.0.0250169.CrossRefPubMed Bustin S a: Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol. 2000, 25: 169-193. 10.1677/jme.0.0250169.CrossRefPubMed
28.
go back to reference Zeisel A, Yitzhaky A, Koerner C, Lauriola M, Cohen-Dvashi H, Köstler WJ, Yarden Y, Wiemann S, Domany E: CMA: A Desktop Application for Quantitative Collective Cell Migration Analysis. J Biomol Screen. 2012, 5-10. Zeisel A, Yitzhaky A, Koerner C, Lauriola M, Cohen-Dvashi H, Köstler WJ, Yarden Y, Wiemann S, Domany E: CMA: A Desktop Application for Quantitative Collective Cell Migration Analysis. J Biomol Screen. 2012, 5-10.
29.
go back to reference Agelopoulos K, Greve B, Schmidt H, Pospisil H, Kurtz S, Bartkowiak K, Andreas A, Wieczorek M, Korsching E, Buerger H, Brandt B: Selective regain of egfr gene copies in model MDA-MB-468. BMC Cancer. 2010, 10: e78-10.1186/1471-2407-10-78.CrossRef Agelopoulos K, Greve B, Schmidt H, Pospisil H, Kurtz S, Bartkowiak K, Andreas A, Wieczorek M, Korsching E, Buerger H, Brandt B: Selective regain of egfr gene copies in model MDA-MB-468. BMC Cancer. 2010, 10: e78-10.1186/1471-2407-10-78.CrossRef
30.
go back to reference Tidow N, Boecker A, Schmidt H, Agelopoulos K, Boecker W, Buerger H:Distinct Amplification of an Untranslated Regulatory Sequence in the egfr Gene Contributes to Early Steps in Breast Cancer Development Advances in Brief Distinct Amplification of an Untranslated Regulatory Sequence in the egfr Gene Contributes to Early St. Cancer Res. 2003, 63 (6): 1172-1178.PubMed Tidow N, Boecker A, Schmidt H, Agelopoulos K, Boecker W, Buerger H:Distinct Amplification of an Untranslated Regulatory Sequence in the egfr Gene Contributes to Early Steps in Breast Cancer Development Advances in Brief Distinct Amplification of an Untranslated Regulatory Sequence in the egfr Gene Contributes to Early St. Cancer Res. 2003, 63 (6): 1172-1178.PubMed
31.
go back to reference Cortez BDA, Quassollo G, Caceres A, Machado-Santelli GM: The fate of chrysotile-induced multipolar mitosis and aneuploid population in cultured lung cancer cells. PLoS One. 2011, 6: e18600-10.1371/journal.pone.0018600.CrossRef Cortez BDA, Quassollo G, Caceres A, Machado-Santelli GM: The fate of chrysotile-induced multipolar mitosis and aneuploid population in cultured lung cancer cells. PLoS One. 2011, 6: e18600-10.1371/journal.pone.0018600.CrossRef
32.
go back to reference Hirsch FR, Varella-Garcia M, McCoy J, West H, Xavier AC, Gumerlock P, Crowley J, Gandara DR, Bunn P a, Franklin W a: Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: a Southwest Oncology Group Study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2005, 23: 6838-6845. 10.1200/JCO.2005.01.2823.CrossRef Hirsch FR, Varella-Garcia M, McCoy J, West H, Xavier AC, Gumerlock P, Crowley J, Gandara DR, Bunn P a, Franklin W a: Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: a Southwest Oncology Group Study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2005, 23: 6838-6845. 10.1200/JCO.2005.01.2823.CrossRef
33.
go back to reference Varella-Garcia M: Stratification of non-small cell lung cancer patients for therapy with epidermal growth factor receptor inhibitors: the EGFR fluorescence in situ hybridization assay. Diagn Pathol. 2006, 1: 19-10.1186/1746-1596-1-19.PubMedCentralCrossRefPubMed Varella-Garcia M: Stratification of non-small cell lung cancer patients for therapy with epidermal growth factor receptor inhibitors: the EGFR fluorescence in situ hybridization assay. Diagn Pathol. 2006, 1: 19-10.1186/1746-1596-1-19.PubMedCentralCrossRefPubMed
34.
go back to reference Sekido Y, Fong KM, Minna JD: Molecular genetics of lung cancer. Annu Rev Med. 2003, 54: 73-87. 10.1146/annurev.med.54.101601.152202.CrossRefPubMed Sekido Y, Fong KM, Minna JD: Molecular genetics of lung cancer. Annu Rev Med. 2003, 54: 73-87. 10.1146/annurev.med.54.101601.152202.CrossRefPubMed
35.
go back to reference Giaccone G, Johnson BE, Eberhard D a: Biomarkers of response to epidermal growth factor receptor inhibitors in Non-Small-Cell Lung Cancer Working Group: standardization for use in the clinical trial setting. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2008, 26: 983-994. 10.1200/JCO.2007.12.9858.CrossRef Giaccone G, Johnson BE, Eberhard D a: Biomarkers of response to epidermal growth factor receptor inhibitors in Non-Small-Cell Lung Cancer Working Group: standardization for use in the clinical trial setting. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2008, 26: 983-994. 10.1200/JCO.2007.12.9858.CrossRef
36.
go back to reference Maegawa M, Takeuchi K, Funakoshi E, Kawasaki K, Nishio K, Shimizu N, Ito F: Growth stimulation of non-small cell lung cancer cell lines by antibody against epidermal growth factor receptor promoting formation of ErbB2/ErbB3 heterodimers. Molecular cancer research: MCR. 2007, 5: 393-401. 10.1158/1541-7786.MCR-06-0303.CrossRefPubMed Maegawa M, Takeuchi K, Funakoshi E, Kawasaki K, Nishio K, Shimizu N, Ito F: Growth stimulation of non-small cell lung cancer cell lines by antibody against epidermal growth factor receptor promoting formation of ErbB2/ErbB3 heterodimers. Molecular cancer research: MCR. 2007, 5: 393-401. 10.1158/1541-7786.MCR-06-0303.CrossRefPubMed
37.
go back to reference Stoscheck CM, Carpenter G:Down Regulation of Epidermal Growth Factor Receptors: Fibroblasts Direct Demonstration of Receptor Degradation in Human. J Cell Biol. 1984, 98 (3): 1058-1053.CrossRef Stoscheck CM, Carpenter G:Down Regulation of Epidermal Growth Factor Receptors: Fibroblasts Direct Demonstration of Receptor Degradation in Human. J Cell Biol. 1984, 98 (3): 1058-1053.CrossRef
38.
go back to reference Beguinot L, Lyall RM, Willingham MC, Pastan I: Down-regulation of the epidermal growth factor receptor in KB cells is due to receptor internalization and subsequent degradation in lysosomes. Proc Natl Acad Sci USA. 1984, 81: 2384-2388. 10.1073/pnas.81.8.2384.PubMedCentralCrossRefPubMed Beguinot L, Lyall RM, Willingham MC, Pastan I: Down-regulation of the epidermal growth factor receptor in KB cells is due to receptor internalization and subsequent degradation in lysosomes. Proc Natl Acad Sci USA. 1984, 81: 2384-2388. 10.1073/pnas.81.8.2384.PubMedCentralCrossRefPubMed
39.
go back to reference Hofman EG, Bader AN, Voortman J, Van den Heuvel DJ, Sigismund S, Verkleij AJ, Gerritsen HC, Henegouwen PMP VBe: Ligand-induced EGF receptor oligomerization is kinase-dependent and enhances internalization. J Biol Chem. 2010, 285: 39481-39489. 10.1074/jbc.M110.164731.PubMedCentralCrossRefPubMed Hofman EG, Bader AN, Voortman J, Van den Heuvel DJ, Sigismund S, Verkleij AJ, Gerritsen HC, Henegouwen PMP VBe: Ligand-induced EGF receptor oligomerization is kinase-dependent and enhances internalization. J Biol Chem. 2010, 285: 39481-39489. 10.1074/jbc.M110.164731.PubMedCentralCrossRefPubMed
40.
go back to reference Friedman LM, Rinon A, Schechter B, Lyass L, Lavi S, Bacus SS, Sela M, Yarden Y: Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: implications for cancer immunotherapy. Proc Natl Acad Sci USA. 2005, 102: 1915-1920. 10.1073/pnas.0409610102.PubMedCentralCrossRefPubMed Friedman LM, Rinon A, Schechter B, Lyass L, Lavi S, Bacus SS, Sela M, Yarden Y: Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: implications for cancer immunotherapy. Proc Natl Acad Sci USA. 2005, 102: 1915-1920. 10.1073/pnas.0409610102.PubMedCentralCrossRefPubMed
41.
go back to reference Oliveira S, Schiffelers RM, Van der Veeken J, Van der Meel R, Vongpromek R, Van Bergen En Henegouwen PMP, Storm G, Roovers RC: Downregulation of EGFR by a novel multivalent nanobody-liposome platform. Journal of controlled release: official journal of the Controlled Release Society. 2010, 145: 165-175. 10.1016/j.jconrel.2010.03.020.CrossRef Oliveira S, Schiffelers RM, Van der Veeken J, Van der Meel R, Vongpromek R, Van Bergen En Henegouwen PMP, Storm G, Roovers RC: Downregulation of EGFR by a novel multivalent nanobody-liposome platform. Journal of controlled release: official journal of the Controlled Release Society. 2010, 145: 165-175. 10.1016/j.jconrel.2010.03.020.CrossRef
42.
go back to reference Nishimura Y, Bereczky B, Ono M: The EGFR inhibitor gefitinib suppresses ligand-stimulated endocytosis of EGFR via the early/late endocytic pathway in non-small cell lung cancer cell lines. Histochem Cell Biol. 2007, 127: 541-553. 10.1007/s00418-007-0281-y.CrossRefPubMed Nishimura Y, Bereczky B, Ono M: The EGFR inhibitor gefitinib suppresses ligand-stimulated endocytosis of EGFR via the early/late endocytic pathway in non-small cell lung cancer cell lines. Histochem Cell Biol. 2007, 127: 541-553. 10.1007/s00418-007-0281-y.CrossRefPubMed
43.
go back to reference Bost F, McKay R, Dean N, Mercola D: The JUN kinase/stress-activated protein kinase pathway is required for epidermal growth factor stimulation of growth of human A549 lung carcinoma cells. J Biol Chem. 1997, 272: 33422-33429. 10.1074/jbc.272.52.33422.CrossRefPubMed Bost F, McKay R, Dean N, Mercola D: The JUN kinase/stress-activated protein kinase pathway is required for epidermal growth factor stimulation of growth of human A549 lung carcinoma cells. J Biol Chem. 1997, 272: 33422-33429. 10.1074/jbc.272.52.33422.CrossRefPubMed
44.
go back to reference Hou M-F, Kuo H-C, Li J-H, Wang Y-S, Chang C-C, Chen K-C, Chen W-C, Chiu C-C, Yang S, Chang W-C:Orai1/CRACM1 overexpression suppresses cell proliferation via attenuation of the store-operated calcium influx-mediated signalling pathway in A549 lung cancer cells. Biochim Biophys Acta. 1810, 2011: 1278-1284. Hou M-F, Kuo H-C, Li J-H, Wang Y-S, Chang C-C, Chen K-C, Chen W-C, Chiu C-C, Yang S, Chang W-C:Orai1/CRACM1 overexpression suppresses cell proliferation via attenuation of the store-operated calcium influx-mediated signalling pathway in A549 lung cancer cells. Biochim Biophys Acta. 1810, 2011: 1278-1284.
45.
go back to reference Puri N, Salgia R: Synergism of EGFR and c-Met pathways, cross-talk and inhibition, in non-small cell lung cancer. Journal of carcinogenesis. 2008, 7: e9-10.4103/1477-3163.44372.CrossRef Puri N, Salgia R: Synergism of EGFR and c-Met pathways, cross-talk and inhibition, in non-small cell lung cancer. Journal of carcinogenesis. 2008, 7: e9-10.4103/1477-3163.44372.CrossRef
46.
go back to reference Stommel JM, Kimmelman AC, Ying H, Nabioullin R, Ponugoti AH, Wiedemeyer R, Stegh AH, Bradner JE, Ligon KL, Brennan C, Chin L, DePinho R a: Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science (New York, N.Y.). 2007, 318: 287-290. 10.1126/science.1142946.CrossRef Stommel JM, Kimmelman AC, Ying H, Nabioullin R, Ponugoti AH, Wiedemeyer R, Stegh AH, Bradner JE, Ligon KL, Brennan C, Chin L, DePinho R a: Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science (New York, N.Y.). 2007, 318: 287-290. 10.1126/science.1142946.CrossRef
47.
go back to reference Guo A, Villén J, Kornhauser J, Stokes MP, Rikova K, Possemato A, Nardone J, Innocenti G, Wetzel R, Wang Y, MacNeill J, Mitchell J, Gygi SP, Rush J, Polakiewicz RD, Comb MJ, Lee K a: Signaling networks assembled by oncogenic EGFR and c-Met. Proc Natl Acad Sci USA. 2008, 105: 692-697. 10.1073/pnas.0707270105.PubMedCentralCrossRefPubMed Guo A, Villén J, Kornhauser J, Stokes MP, Rikova K, Possemato A, Nardone J, Innocenti G, Wetzel R, Wang Y, MacNeill J, Mitchell J, Gygi SP, Rush J, Polakiewicz RD, Comb MJ, Lee K a: Signaling networks assembled by oncogenic EGFR and c-Met. Proc Natl Acad Sci USA. 2008, 105: 692-697. 10.1073/pnas.0707270105.PubMedCentralCrossRefPubMed
48.
go back to reference Denlinger CE, Ikonomidis JS, Reed CE, Spinale FG: Epithelial to mesenchymal transition: the doorway to metastasis in human lung cancers. J Thorac Cardiovasc Surg. 2010, 140: 505-513. 10.1016/j.jtcvs.2010.02.061.CrossRefPubMed Denlinger CE, Ikonomidis JS, Reed CE, Spinale FG: Epithelial to mesenchymal transition: the doorway to metastasis in human lung cancers. J Thorac Cardiovasc Surg. 2010, 140: 505-513. 10.1016/j.jtcvs.2010.02.061.CrossRefPubMed
49.
go back to reference Peter Y, Comellas A, Levantini E, Ingenito EP: Steven D:Epidermal growth factor receptor and claudin-2 participate in A549 permeability and remodeling: implicationsfor non-small cell lung cancer tumor colonization. Mol. Carcinog. 2009, 48: 488-497. 10.1002/mc.20485.PubMedCentralCrossRefPubMed Peter Y, Comellas A, Levantini E, Ingenito EP: Steven D:Epidermal growth factor receptor and claudin-2 participate in A549 permeability and remodeling: implicationsfor non-small cell lung cancer tumor colonization. Mol. Carcinog. 2009, 48: 488-497. 10.1002/mc.20485.PubMedCentralCrossRefPubMed
50.
go back to reference Manelli-Oliveira R, Machado-Santelli GM:Cytoskeletal and nuclear alterations in human lung tumor cells: a confocal microscope study. Histochem Cell Biol. 2001, 115 (5): 403-411.PubMed Manelli-Oliveira R, Machado-Santelli GM:Cytoskeletal and nuclear alterations in human lung tumor cells: a confocal microscope study. Histochem Cell Biol. 2001, 115 (5): 403-411.PubMed
51.
go back to reference Holz C, Niehr F, Boyko M, Hristozova T, Distel L, Budach V, Tinhofer I: Epithelial-mesenchymal-transition induced by EGFR activation interferes with cell migration and response to irradiation and cetuximab in head and neck cancer cells. Radiother Oncol. 2011, 101: 158-164. 10.1016/j.radonc.2011.05.042.CrossRefPubMed Holz C, Niehr F, Boyko M, Hristozova T, Distel L, Budach V, Tinhofer I: Epithelial-mesenchymal-transition induced by EGFR activation interferes with cell migration and response to irradiation and cetuximab in head and neck cancer cells. Radiother Oncol. 2011, 101: 158-164. 10.1016/j.radonc.2011.05.042.CrossRefPubMed
Metadata
Title
Independent of ErbB1 gene copy number, EGF stimulates migration but is not associated with cell proliferation in non-small cell lung cancer
Authors
Camila Lauand
Paula Rezende-Teixeira
Beatriz Araújo Cortez
Evandro Luís de Oliveira Niero
Gláucia Maria Machado-Santelli
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2013
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-13-38

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