Transformation of NIH 3T3 Cells by HER3 or HER4 Receptors Requires the Presence of HER1 or HER2

Abstract

Members of the epidermal growth factor receptor (EGFR) subfamily of receptor protein tyrosine kinases have been implicated in the pathogenesis of various malignancies. The ability of one EGFR subfamily member to influence, or function synergistically with, another is likely to be a general feature of these receptors. To assess the role of receptor heterodimerization, we analyzed the ability of Neu differentiation factor (NDF) to induce cell growth and transformation of NIH 3T3 cells transfected with different combinations of the EGFR subfamily of receptors. NDF induced mitogenesis, but not transformation, of cells expressing either HER3 or HER4 alone. However, NDF-induced cell transformation was observed when either HER1 or HER2 was coexpressed with HER3 or HER4. In analogous receptor phosphorylation experiments, NDF-induced transphosphorylation appears to be correlated with synergistic transformation of NIH 3T3 cells. Interestingly, transphosphorylation between HER1 and HER4 can be stimulated by either EGF or NDF.

Effects of oncogenic ErbB2 on G1 cell cycle regulators in breast tumour cells

“…It was recently shown in a transgenic model of Neu-induced mammary cancer that tumour progression was associated with a dramatic increase in ErbB3 tyrosine phosphorylation (Siegel et al, 1999). Moreover, the ErbB2/ErbB3 heterodimer appears to be the most potent ErbB signalling complex in terms of in vitro growth and transformation (Alimandi et al, 1995;Pinkas-Kramarski et al, 1996;Zhang et al, 1996;Waterman et al, 1999). ErbB3 couples well to the PI3K pathway due to the multiple binding sites for p85 (Fedi et al, 1994;Prigent and Gullick, 1994).…”

Suppression of breast cancer cell growth by a monoclonal antibody targeting cleavable ErbB4 isoforms

“…The lysates were either boiled or not boiled at 95 1C for 5 min in sample buffer with or without DTT and analysed by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting, as previously described (Kainulainen et al, 2000). ErbB expression in NIH 3T3-7d (Zhang et al, 1996) and NR6 (Sundvall et al, submitted) transfectants was analysed by western blotting under nonreducing conditions using 1:1000 dilution of anti-ErbB1 (sc-03), anti-ErbB2 (sc-284), anti-ErbB3 (sc-285) (all stocks 0.2 mg/ml; Santa Cruz Biotechnology) or mAb 1479 (stock 1.25 mg/ml).…”

The oncogenic ErbB-2/ErbB-3 heterodimer is a surrogate receptor of the epidermal growth factor and betacellulin

“…Unlike ErbB-3 homodimers, that are functionally inactive (Riese et al, 1995;Pinkas-Kramarski et al, 1996b), ErbB-2/ErbB-3 heterodimers appear to be the predominant receptor of NDF in carcinoma cells . Consistent with the high stability and potent proliferative action of this complex, coexpression of ErbB-2 and ErbB-3 confers a transformed phenotype (Alimandi et al, 1995;Wallasch et al, 1995), whose potency in ®broblasts is second only to an ErbB-1/ErbB-2 heterodimer (Cohen et al, 1996;Zhang et al, 1996).…”