EGF and IGF-I Synergistically Stimulate Proliferation of Human Esophageal Epithelial Cells

Qureshi, Faisal; Tchórzewski, Marcin; Duncan, Mark D.; Harmon, John W.

doi:10.1006/jsre.1997.5080

Cited by 37 publications

(11 citation statements)

References 3 publications

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“…The in vitro biological effects of IGFs are potentiated in the presence of other hormones or growth factors (Table 1), and these phenomena are also observed in vivo. In the beginning stages of studies on the biological activities of IGFs using fibroblasts, platelet-derived growth factor (PDGF), epidermal growth factor (EGF) or fibroblast growth factor (FGF) were shown to prime the cells to IGFs for cell proliferation (Stiles et al 1979, Qureshi et al 1997. These growth factors induce activation of protein kinase (PKC) or expression of proto-oncogenes, such as c-fos and c-jun, preparing the cell to be ready for cell cycle progression in response to IGFs.…”

Section: Modulation Of Igf Signaling Amplification Of Igf Signalingmentioning

confidence: 99%

40 YEARS OF IGF1: IGF1 receptor signaling pathways

Hakuno

Takahashi

2018

Journal of Molecular Endocrinology

305

238

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Insulin-like growth factors (IGFs) bind specifically to the IGF1 receptor on the cell surface of targeted tissues. Ligand binding to the α subunit of the receptor leads to a conformational change in the β subunit, resulting in the activation of receptor tyrosine kinase activity. Activated receptor phosphorylates several substrates, including insulin receptor substrates (IRSs) and Src homology collagen (SHC). Phosphotyrosine residues in these substrates are recognized by certain Src homology 2 (SH2) domain-containing signaling molecules. These include, for example, an 85 kDa regulatory subunit (p85) of phosphatidylinositol 3-kinase (PI 3-kinase), growth factor receptor-bound 2 (GRB2) and SH2-containing protein tyrosine phosphatase 2 (SHP2/Syp). These bindings lead to the activation of downstream signaling pathways, PI 3-kinase pathway and Ras-mitogen-activated protein kinase (MAP kinase) pathway. Activation of these signaling pathways is known to be required for the induction of various bioactivities of IGFs, including cell proliferation, cell differentiation and cell survival. In this review, the well-established IGF1 receptor signaling pathways required for the induction of various bioactivities of IGFs are introduced. In addition, we will discuss how IGF signals are modulated by the other extracellular stimuli or by themselves based on our studies.

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Section: Modulation Of Igf Signaling Amplification Of Igf Signalingmentioning

confidence: 99%

40 YEARS OF IGF1: IGF1 receptor signaling pathways

Hakuno

Takahashi

2018

Journal of Molecular Endocrinology

305

238

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“…26 Thus, EGF may positively regulate the IGF signaling pathway through inhibition of IGFBP-3, 25,26 accounting for a synergistic effect of IGF-I and EGF upon esophageal epithelial cells. 27,28 IGFBP-3 inhibition by RNA interference augments cell proliferation in TE11 esophageal cancer cells implying the growth inhibitory role of IGFBP-3. 25 These observations, however, do not unravel the role of IGFBP-3 overexpression in esophageal cancer.…”

Section: Introductionmentioning

confidence: 99%

IGFBP-3 regulates esophageal tumor growth through IGF-dependent and independent mechanisms

Takaoka

Kim

Okawa

et al. 2007

Cancer Biology & Therapy

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Insulin-like growth factor binding protein (IGFBP)-3 exerts either proapoptotic or growth stimulatory effects depending upon the cellular context. IGFBP-3 is overexpressed frequently in esophageal cancer. Yet, the role of IGFBP-3 in esophageal tumor biology remains elusive. To delineate the functional consequences of IGFBP-3 overexpression, we stably transduced Ha-Ras V12 -transformed human esophageal cells with either wild-type or mutant IGFBP-3, the latter incapable of binding Insulin-like growth factor (IGFs) as a result of substitution of amino-terminal Ile 56 , Leu 80 , and Leu 81 residues with Glycine residues. Wild-type, but not mutant, IGFBP-3 prevented IGF-I from activating the IGF-1 receptor and AKT, and suppressed anchorage-independent cell growth. When xenografted in nude mice, in vivo bioluminescence imaging demonstrated that wild-type, but not mutant IGFBP-3, abrogated tumor formation by the Ras-transformed cells with concurrent induction of apoptosis, implying a prosurvival effect of IGF in cancer cell adaptation to the microenvironment. Moreover, there was more aggressive tumor growth by mutant IGFBP-3 overexpressing cells than control cell tumors, without detectable caspase-3 cleavage in tumor tissues, indicating an IGF-independent growth stimulatory effect of mutant IGFBP-3. In aggregate, these data suggest that IGFBP-3 contributes to esophageal tumor development and progression through IGF-dependent and independent mechanisms.

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“…The same results were later replicated in immortalized oesophageal cells (HET‐1A cell line). In this experiment, EGF, IGF‐I and IGF‐I/BP‐3 all enhanced HET‐1A proliferation 15 . The combination of EGF and IGF‐I was most effective (Fig.…”

Section: Growth Factors and Oesophageal Repairmentioning

confidence: 66%

Role of growth factors in oesophageal mucosal healing: A work in progress

Younes¹,

Duncan²,

Harmon³

1998

J of Gastro and Hepatol

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Reflux of gastroduodenal contents into the oesophagus results in dynamic cycles of injury followed by cell proliferation and repair. These processes are receiving increased attention due to the high incidence of gastro‐oesophageal reflux disease and the rising incidence of adenocarcinoma of the oesophagus. Repeated cycles of injury and repair may lead to abnormal differentiation followed by abnormal growth. This article summarizes the research performed by our group in the field of oesophageal injury and repair. We initially developed an in vivo perfused rabbit oesophagus model that served to study the effects of various components of the gastroduodenal juice on several parameters of oesophageal injury. We have shown that pepsin causes severe morphological oesophagitis at an acidic pH but is ineffective at an alkaline pH. We have also demonstrated that trypsin causes severe morphological oesophagitis at an alkaline pH but not at an acidic pH. Bile salts were found to disrupt the oesophageal barrier at both pH levels. We have also studied the effects of epidermal growth factor (EGF) and insulin‐like growth factor‐I (IGF‐I) on oesophageal regeneration. We used an ex vivo oesophageal explant model for these experiments. Both EGF and IGF‐I cause a dose‐dependent increase in oesophageal DNA synthesis, cell proliferation and mucosal growth. These effects are synergistic and can be inhibited by specific tyrphostins. We are currently studying the role of growth factors as therapeutic agents and the role of growth factors in the development of Barrett’s oesophagus and adenocarcinoma.

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EGF and IGF-I Synergistically Stimulate Proliferation of Human Esophageal Epithelial Cells

Cited by 37 publications

References 3 publications

40 YEARS OF IGF1: IGF1 receptor signaling pathways

40 YEARS OF IGF1: IGF1 receptor signaling pathways

IGFBP-3 regulates esophageal tumor growth through IGF-dependent and independent mechanisms

Role of growth factors in oesophageal mucosal healing: A work in progress

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