Epidermal growth factor, but not hepatocyte growth factor, suppresses the apoptosis induced by transforming growth factor‐beta in fetal hepatocytes in primary culture

“…Indeed, we and others have previously reported that EGF induces proliferation [20] and protects hepatocytes from various apoptotic insults, including TGF-β, Fas, and deoxycholic acid [25,35,36].…”

Section: It Is Well Known That Egfr-dependent Signalling Integrates Pmentioning

confidence: 75%

EGFR is dispensable for c-Met-mediated proliferation and survival activities in mouse adult liver oval cells

Martínez-Palacián

Castillo

Herrera

et al. 2012

Cellular Signalling

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“…However, the role of EGF in the promotion of cell survival has only been reported in a limited number of cases. For example, EGF suppresses apoptosis induced by transforming growth factor b (TGFb) in primary hepatocytes (Fabregat et al, 1996). In mammary epithelial cells, apoptosis induced by a combination of serum-free medium and high cell density is prevented by EGF (Merlo et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Leu¹,

Chang²,

Hu³

2000

Oncogene

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Overexpression of epidermal growth factor receptor (EGFR) and establishment of transforming growth factor a (TGF a)/EGF autocrine system are frequently detected in tumor cells. In addition to mitogenic ability, we demonstrate in this report that EGF protects a human esophageal carcinoma (CE) cell line, CE81T/VGH, from staurosporine-induced apoptosis. The anti-apoptotic signal of EGF is alleviated by a MEK inhibitor PK98059 or an ERK2 dominant negative mutant but not by a phosphatidylinositol-3'-kinase (PI-3K) inhibitor wortmannin. Furthermore, v-raf blocks apoptosis induced by staurosporine. This evidence implies that the survival signal of EGF is mediated via the Raf-MEK-ERK pathway but not the PI3-K pathway. The survival e ect of EGF is coincident with the induction of mcl-1, an antiapoptotic gene in the bcl-2 family. PD98059 also suppresses the induction of Mcl-1 by EGF, implying that EGF may up-regulate Mcl-1 via the MAP kinase pathway. Overexpression of mcl-1 is su cient to protect against apoptosis, while transfection of a mcl-1 antisense plasmid causes cell death. The expression of mcl-1 antisense plasmid also suppresses the anti-apoptotic e ect of EGF. Taken together, these results indicate that EGF may up-regulate Mcl-1 through the MAP kinase pathway to suppress apoptosis.

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“…Furthermore, growth factors may also contribute towards cell survival since growth factor withdrawal can lead to apoptosis (Oltvai et al, 1993;White 1996). There are numerous examples demonstrating that EGF can prevent apoptosis in response to a wide variety of stimuli (Coles et al, 1993;Luciano et al, 1994;Nakajima et al, 1994;Fabregat et al, 1996;Garcia-Lloret et al, 1996), and inhibition of EGFR expression can induce apoptosis (Englert et al, 1995). Since activation of EGFRs may be involved in stimulating colonic epithelium proliferation and in antagonizing apoptosis, one potential mechanism to suppress colorectal cancer may include modulation of apoptotic pathway(s) by inhibiting EGFR using anti-EGFR mAbs.…”

mentioning

confidence: 99%

Nuclear targeting of Bax during apoptosis in human colorectal cancer cells

et al. 1998

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Homeostasis in colonic epithelial cells is regulated by the balance between proliferative activity and cell loss by apoptosis. Because epithelial cells at the apex of colonic crypts undergo apoptosis and proliferative activity is usually restricted to the base of the crypts, it has been proposed that the limited availability of growth factorsignals at the upper portions of the crypts may trigger apoptosis. In the present studies, we investigate the mechanism of apoptosis mediated by growth factor deprivation in colorectal carcinoma cells by delineating the possible involvement of Bax and its subcellular localization. We report that inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase activity and downregulation of EGFR by anti-EGFR mAb 225 induces apoptosis in human colorectal carcinoma DiFi and FET cells. Induction of apoptosis was preceded by enhanced expression of newly synthesized Bax protein, and required protein synthesis. In the mAb 225-treated cells, Bax was redistributed from the cytosol to the nucleus and subsequently, to the nuclear membranes. The observed induction of Bax expression by mAb 225 was not associated with p53 induction. However, mAb 225 treatment also triggered relocalization of p53 from the cytosol to a nuclear membrane-bound form. Induction of Bax and its redistribution to the nucleus of DiFi cells during apoptosis was also demonstrated in response to butyrate, a physiological relevant molecule in colonic epithelial cells as it is the principal short-chain fatty acid produced by bacterial fermentation of dietary ®ber in colonic epithelium. Using immuno¯uorescence and confocal microscopy, we observed that Bax is predominantly localized in the cytosol, but during apoptosis it is localized both inside and along the nuclear membrane. Taken together, these ®ndings suggest that apoptosis induced by growth factor-deprivation or butyrate may involve the subcellular redistribution of Bax in human colorectal carcinoma cells.

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Epidermal growth factor, but not hepatocyte growth factor, suppresses the apoptosis induced by transforming growth factor‐beta in fetal hepatocytes in primary culture

Cited by 68 publications

References 31 publications

EGFR is dispensable for c-Met-mediated proliferation and survival activities in mouse adult liver oval cells

EGFR is dispensable for c-Met-mediated proliferation and survival activities in mouse adult liver oval cells

Epidermal growth factor (EGF) suppresses staurosporine-induced apoptosis by inducing mcl-1 via the mitogen-activated protein kinase pathway

Nuclear targeting of Bax during apoptosis in human colorectal cancer cells

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