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

Abstract

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.

Expression, localization, and regulation of the neuregulin receptor ErbB3 in mouse heart

“…Prigent et al (1992) reported an immunohistochemical and Northern blot study on normal adult and fetal tissues and found that ErbB3 was expressed in the adult heart. In the late 1990s, however, a series of studies in neonatal and adult cardiac hearts concluded that ErbB4 and ErbB2 were the principal receptor and partner, respectively, of NRG‐1β in the heart (Sundaresan et al, 1998; Zhao et al, 1998; Rohrbach et al, 1999). ErbB3 was shown to be expressed during embryonic stages but to be switched off after birth (Zhao et al, 1998).…”

“…To date, only the expression of ErbB1, ErbB2, and ErbB4 has been documented in the adult heart (Sundaresan et al, 1998; Zhao et al, 1998; Rohrbach et al, 1999). ErbB3 is expressed during embryonic stages but not in the adult heart (Zhao et al, 1998).…”

Laminin-1 and epidermal growth factor family members co-stimulate fetal pancreas cell proliferation and colony formation

“…In vitro , BTC stimulates proliferation of the rat insulinoma cell line INS‐1, but not of the less differentiated line, RINm5F (Huotari et al, 1998). BTC also promotes proliferation of a fetal rat pancreatic epithelial cell line, BUD (Sundaresan et al, 1998). EGF itself increases proliferation of mesenchyme‐free rat pancreatic epithelium at embryonic day (E) 13, while preventing endocrine cell differentiation (Cras‐Meneur et al, 2001).…”

Allograft Acceptance Despite Differential Strain-Specific Induction of TGF-Ƴ/IL-10-MediatedImmunoregulation

“…Real‐time PCR has been described in detail by other investigators (23–26). This technique uses an oligonucleotide hybridization probe that is labeled with a reporter fluorescent dye (6‐carboxy‐fluorescein) at the 5′ end and with a quencher fluorescent dye (6‐carboxy‐tetramethylrhodamine) at the 3′ end.…”