Localization of epidermal growth factor receptor in hepatocyte nuclei

Abstract

Experiments undertaken to investigate the binding of epidermal growth factor by hepatocyte nuclei showed that: (a) isolated nuclei from both normal and regenerating rat liver are capable of binding 125I-epidermal growth factor, (b) the nuclear epidermal growth factor-binding protein is similar in molecular weight to the plasma membrane epidermal growth factor receptor, (c) monoclonal antibodies produced against the plasma membrane epidermal growth factor receptor recognize the nuclear epidermal growth factor receptor and (d) the nuclear receptor has an affinity for epidermal growth factor comparable to that of the plasma membrane receptor, but fewer (approximately 10%) nuclear receptors are available per protein unit compared with the plasma membrane.

Nuclear EGFR signalling network in cancers: linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival

“…Furthermore, nuclear expression of EGFR positively correlates with that of Ki-67, an indicator of active proliferation (Lo et al, 2005c). A casual correlation of nuclear accumulation of EGFR/mouse erbb1 and their ligands EGF/TGF-a with cell proliferation/DNA synthesis has been reported by several studies (Marti et al, 1991;Schausberger et al, 2003). In agreement with its role in proliferation/DNA synthesis, EGFR undergoes nuclear translocalization in regenerating livers (Marti et al, 1991), pregnant uterus and proliferative basal cells within normal mouth mucosa (Lin et al, 2001).…”

“…Nuclear detection of EGFR was first reported in hepatocytes that underwent regeneration and in primary adrenocortical carcinomas more than a decade ago (Kamio et al, 1990;Marti et al, 1991). Nuclear expression of EGFR was further detected in other cell types and tissues, such as placentas, thyroids and immortalized epithelial cells of ovary and kidney origins (Cao et al, 1995;Lin et al, 2001;Marti et al, 2001;Lo et al, 2005a).…”

“…A cellular mechanism that can potentially account for nuclear import of receptor tyrosine kinases (RTKs) is also proposed recently (Giri et al, 2005). It is important to note that nuclear import is not only observed with EGFR but also with many other RTKs, including mouse erbb1, HER-2, rat p185neu, HER-3, truncated C-terminal HER-4, and fibroblast growth factor receptor (FGFR) and cytokine receptors (Marti et al, 1991;Xie and Hung, 1994;Lin et al, 2001;Ni et al, 2001;Offterdinger et al, 2002;Schausberger et al, 2003;Wang et al, 2004;Krolewski, 2005). As RTK-mediated pathways are frequently deregulated in many human cancers and are closely linked to tumorigenesis and tumour progression, it is thus an urgent task to better understand the nature of these nuclear RTKs and, more importantly, to determine the extent to which they contribute to the malignant biology and therapeutic response of human cancers.…”

“…Albeit very little is known about physiological function and cancer relevance of the nuclear EGFR pathway until recent years, EGFR has been consistently detected in the nuclei of cancer cells and primary tumour specimens of various origins as well as in those of other highly proliferative tissues (Marti et al, 1991;Cao et al, 1995;Lin et al, 2001;Lo et al, 2005a, b). Increased expression of nuclear EGFR is linked to poor clinical outcome in patients with breast carcinomas (Lo et al, 2005c) and oropharyngeal squamous cell carcinomas (Psyrri et al, 2005).…”

Sex difference in immunostaining of RET in the adult mouse kidney

“…Using a variety of techniques, other transmembrane receptors have been shown to be translocated to the nucleus upon stimulation by the ligands. These include insulin receptors (Podlecki et al, 1987), epidermal growth factor receptors (Rakowicz-Szulczynska et al, 1989;Jiang and Schindler, 1990;Marti et al,1991;Holt et al, 1994), HER2 (Xie and Hung, 1994) and IL-1 receptors (Curtis et al, 1990). Similar experiments can be done on nuclei preparation from female mouse kidneys to con®rm the nuclear localization of RET and to identify other protein(s) which may bind to RET and directs its intracellular localization.…”