This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sundaresan, S. Articles by Mather, J. P. Search for Related Content PubMed PubMed Citation Articles by Sundaresan, S. Articles by Mather, J. P.

Biological Response to ErbB Ligands in Nontransformed Cell Lines Correlates with a Specific Pattern of Receptor Expression

Department of Protein Chemistry, Genentech, Inc., South San Francisco, California 94080

Address all correspondence and requests for reprints to: Srividya Sundaresan, Ph.D., 1 DNA Way, MS 45, Genentech, Inc., South San Francisco, California 94080. E-mail: vidya{at}gene.com

The human epidermal growth factor receptor (HER or ErbB) family consists of four distinct members, including the epidermal growth factor (EGF) receptor (EGFR, HER1, or ErbB1), ErbB2 (HER2 or neu), ErbB3 (HER3), and ErbB4 (HER4). Activation of these receptors plays an important role in the regulation of cell proliferation, differentiation, and survival in several different tissues. Binding of a specific ligand to one of the ErbB receptors triggers the formation of specific receptor homo- and heterodimers, with ErbB2 being the preferred signaling partner. We analyzed the levels of various ErbB receptor messenger RNAs in a series of nontransformed cell lines by real time quantitative RT-PCR. The cell lines chosen were derived from a variety of tissues, including pancreas, lung, heart, and nervous system. Further, we measured biological responses in these cell lines upon treatment with EGF, betacellulin, and two types of neuregulins, heregulin and sensory and motor neuron-derived factor. All cell lines examined expressed detectable levels of ErbB2. High levels of expression of ErbB3 were correlated with responsiveness to heregulin and sensory and motor neuron-derived factor, whereas high levels of EGFR expression were correlated with responsiveness to EGF and betacellulin. Moreover, the sensitivity of a cell line to ErbB ligands was also correlated with the levels of expression of the appropriate ErbB receptors in that cell line. These results are consistent with our hypothesis that appropriate biological responsiveness to ErbB ligands is determined by the levels of expression of specific ErbB receptor combinations within a given tissue.

This article has been cited by other articles:

				K. Zscheppang, W. Liu, M. V. Volpe, H. C. Nielsen, and C. E. L. Dammann ErbB4 regulates fetal surfactant phospholipid synthesis in primary fetal rat type II cells Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L429 - L435. [Abstract] [Full Text] [PDF]

				M. S. Gordon, D. Matei, C. Aghajanian, U. A. Matulonis, M. Brewer, G. F. Fleming, J. D. Hainsworth, A. A. Garcia, M. D. Pegram, R. J. Schilder, et al. Clinical Activity of Pertuzumab (rhuMAb 2C4), a HER Dimerization Inhibitor, in Advanced Ovarian Cancer: Potential Predictive Relationship With Tumor HER2 Activation Status J. Clin. Oncol., September 10, 2006; 24(26): 4324 - 4332. [Abstract] [Full Text] [PDF]

				C. R. Sussman, T. Vartanian, and R. H. Miller The ErbB4 Neuregulin Receptor Mediates Suppression of Oligodendrocyte Maturation J. Neurosci., June 15, 2005; 25(24): 5757 - 5762. [Abstract] [Full Text] [PDF]

				D. B. Agus, M. S. Gordon, C. Taylor, R. B. Natale, B. Karlan, D. S. Mendelson, M. F. Press, D. E. Allison, M. X. Sliwkowski, G. Lieberman, et al. Phase I Clinical Study of Pertuzumab, a Novel HER Dimerization Inhibitor, in Patients With Advanced Cancer J. Clin. Oncol., April 10, 2005; 23(11): 2534 - 2543. [Abstract] [Full Text] [PDF]

				K. Dagnon, E. Pacary, F. Commo, M. Antoine, M. Bernaudin, J.-F. Bernaudin, and P. Callard Expression of Erythropoietin and Erythropoietin Receptor in Non-Small Cell Lung Carcinomas Clin. Cancer Res., February 1, 2005; 11(3): 993 - 999. [Abstract] [Full Text] [PDF]

				G. Sithanandam, G. T. Smith, A. Masuda, T. Takahashi, L. M. Anderson, and L. W. Fornwald Cell cycle activation in lung adenocarcinoma cells by the ErbB3/phosphatidylinositol 3-kinase/Akt pathway Carcinogenesis, October 1, 2003; 24(10): 1581 - 1592. [Abstract] [Full Text] [PDF]

				G. D. Leikauf, M. T. Borchers, D. R. Prows, and L. G. Simpson Mucin Apoprotein Expression in COPD* Chest, May 1, 2002; 121(5_suppl): 166S - 182S. [Abstract] [Full Text] [PDF]

				M. K. Lingohr, L. M. Dickson, J. F. McCuaig, S. R. Hugl, D. R. Twardzik, and C. J. Rhodes Activation of IRS-2--Mediated Signal Transduction by IGF-1, but not TGF-{alpha} or EGF, Augments Pancreatic {beta}-Cell Proliferation Diabetes, April 1, 2002; 51(4): 966 - 976. [Abstract] [Full Text] [PDF]

				V. Pawlowski, F. Revillion, M. Hebbar, L. Hornez, and J.-P. Peyrat Prognostic Value of the Type I Growth Factor Receptors in a Large Series of Human Primary Breast Cancers Quantified with a Real-Time Reverse Transcription-Polymerase Chain Reaction Assay Clin. Cancer Res., November 1, 2000; 6(11): 4217 - 4225. [Abstract] [Full Text] [PDF]

				A. M. Feldman, B. H. Lorell, and S. E. Reis Trastuzumab in the Treatment of Metastatic Breast Cancer : Anticancer Therapy Versus Cardiotoxicity Circulation, July 18, 2000; 102(3): 272 - 274. [Abstract] [Full Text] [PDF]