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

• Published in: Endocrinology (Philadelphia) Vol. 139; no. 12; pp. 4756 - 4764
• Main Authors: Sundaresan, Srividya, Roberts, Penelope E, King, Kathleen L, Sliwkowski, Mark X, Mather, Jennie P
• Format: Journal Article
• Language: English
• Published: Washington Endocrine Society 01-12-1998; Oxford University Press
• Subjects: Biological effects; Cell activation; Cell differentiation; Cell lines; Cell proliferation; Cell survival; Correlation; Epidermal growth factor; Epidermal growth factor receptors; ErbB protein; ErbB-1 protein; ErbB-2 protein; ErbB-3 protein; Growth factors; Heregulin; Ligands; Nervous system; Receptors
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.139.12.6378

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.