Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin.

Wu, Xipu; Fan, Zhen; Masui, Hideo; Rosen, Neal; Mendelsohn, John

doi:10.1172/jci117871

Cited by 341 publications

(230 citation statements)

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“…Treatment with mAb 225 also caused a reduction in the viability of DiFi cells by 45% compared to control cells in a timedependent manner ( Figure 1D). These results are consistent with our earlier report that mAb 225-inhibits the growth of DiFi cells (Wu et al, 1995). The observed induction of apoptosis by anti-EGFR mAb 225 was not a restricted phenomenon in DiFi cells with high EGFR (1.5 ± 2610 6 /cell) , as downregulation of EGFR by mAb 225 also induces apoptosis in another colorectal carcinoma FET cells (Figure 2A, upper two blots) which have low EGF binding sites [6.0610 3 , high a nity; 4.26610 4 , low a nity (Huang et al, 1992)].…”

Section: Mab 225 Induces Apoptosis In Colorectal Carcinoma Difi and Fsupporting

confidence: 94%

“…Earlier we showed that inhibition of EGFR tyrosine phosphorylation by anti-EGFR mAb 225 induces apoptosis in DiFi human colorectal carcinoma cells (Wu et al, 1995). In the present study, we investigate the mechanism of EGFR-mediated apoptosis in colorectal carcinoma cells by delineating the involvement of Bax.…”

mentioning

confidence: 81%

“…Human colorectal carcinoma DiFi cells Wu et al, 1995;Mandel and Kumar, 1997) and FET cells (Huang et al, 1992) were maintained in DMEM-F12 (1 : 1) supplemented with 10% fetal calf serum. All experiments were performed with cells in logarithmic phase by controling the plating density.…”

Section: Cell Cultures Cell Extracts and Immunoblottingmentioning

confidence: 99%

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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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Section: Mab 225 Induces Apoptosis In Colorectal Carcinoma Difi and Fsupporting

confidence: 94%

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confidence: 81%

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Nuclear targeting of Bax during apoptosis in human colorectal cancer cells

et al. 1998

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“…For example, stimulation of IL-3 or erythropoietin receptors provides both proliferation and survival signals to hematopoietic precursors (Boyer et al, 1992;Koury and Bondurant, 1988;Silva et al, 1996). Similarly, signaling through EGFR has been shown to promote cell cycle progression, di erentiation and survival of epithelial cells (Merlo et al, 1995;Wu et al, 1995). Blockade of EGFR signaling on benign and tumor epithelial cell lines with neutralizing antibodies directed against this receptor resulted in a cytostatic e ect with or without cell cycle arrest [ (Wu et al, 1995), and references therein.…”

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confidence: 99%

EGF receptor signaling inhibits keratinocyte apoptosis: evidence for mediation by Bcl-XL

et al. 1998

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Signaling through the epidermal growth factor receptor (EGFR) has been primarily implicated in the growth of epithelial cells including keratinocytes. However, the mechanism by which EGFR stimulation promotes keratinocyte cell growth is poorly understood. Here we report that human keratinocytes undergo apoptosis when incubated with the blocking EGFR monoclonal antibody 225 IgG, or PD153035, a highly speci®c EGFR tyrosine kinase inhibitor. Endogenous mRNA and protein levels of Bcl-X L , a member the Bcl-2 family which suppresses apoptosis, were speci®cally inhibited by EGFR blockade. Furthermore, stimulation of EGFR signaling through two natural ligands, transforming growth factor (TGF)-a and epidermal growth factor (EGF), increased the expression of Bcl-X L in quiescent keratinocytes and HaCaT cells. Finally, ectopic expression of Bcl-X L in HaCaT cells increased survival after EGFR blockade when compared to untransfected cells or HaCaT keratinocytes transfected with empty vector. These results suggest that the anti-apoptotic protein Bcl-X L plays an important role in the maintenance of keratinocyte survival in response to EGFR signaling.

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“…However, most cancers involve dysfunction of more than one PTK and crosstalk between their downstream signalling pathways. A therapeutic approach to address this issue involves co-targeting different PTKs (Wu et al, 1995;Ye et al, 1999;Moasser et al, 2001;Moulder et al, 2001;Lu et al, 2001;Chakravarti et al, 2002;Totpal et al, 2002;Camirand et al, 2002). For co-targeting approaches to be useful, careful consideration must be given to the choice of PTKs to be simultaneously blocked (Dancey and Sausville, 2003).…”

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confidence: 99%

Co-targeting IGF-1R and c-kit: synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells

Camirand

Pollak

2004

Br J Cancer

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Most small cell lung cancers (SCLC) coexpress the c-kit protein tyrosine receptor kinase and its ligand stem cell factor, resulting in an autocrine loop. As SCLC growth is also driven by insulin-like growth factor-1 receptor (IGF-1R) signalling, tyrphostins AG 1024 and 1296 (inhibitors of IGF-1R and c-kit activity, respectively) were used to co-target these receptors in H 209 SCLC cells. Combination treatment caused synergy in proliferation inhibition and in apoptosis induction, and also enhanced reduction in phosphorylation of Erk1/Erk2, suggesting that co-targeting IGF-1R and c-kit in SCLC may be more effective than single-agent therapies.

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Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin.

Abstract: Invest. 1995Invest. . 95:1897Invest. -1905

Cited by 341 publications

References 41 publications

Nuclear targeting of Bax during apoptosis in human colorectal cancer cells

Nuclear targeting of Bax during apoptosis in human colorectal cancer cells

EGF receptor signaling inhibits keratinocyte apoptosis: evidence for mediation by Bcl-XL

Co-targeting IGF-1R and c-kit: synergistic inhibition of proliferation and induction of apoptosis in H 209 small cell lung cancer cells

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