Epidermal growth factor receptor-directed enterocyte proliferation does not induce Wnt pathway transcription

Taylor, Janice A.; Bernabe, Kathryn Q.; Guo, Jun; Warner, Brad W.

doi:10.1016/j.jpedsurg.2007.01.032

Cited by 8 publications

(5 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both increased cell production and decreased cell death may suggest an increased gut epithelial cell turnover and may be responsible for increased cell mass in this highly proliferative compartment. Our observations are consistent with the data of other investigators that EGFr activation stimulates cell proliferation and prevents short bowel resectioninduced enterocyte apoptosis [19,20].…”

Section: Discussionsupporting

confidence: 94%

“…Several studies have provided strong support for the crucial role of EGFr signaling as a mediator of adaptation in SBS. Stimulation of this receptor is linked with a magnified adaptation response measured by taller villi, deeper crypts, and augmented enterocyte proliferation [19], whereas attenuation of the activity of this receptor is associated with impaired adaptation [20].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Responsiveness of intestinal epithelial cell turnover to TGF-α after bowel resection in a rat is correlated with EGF receptor expression along the villus–crypt axis

et al. 2007

View full text Add to dashboard Cite

Recent evidence suggests that transforming growth factor alpha (TGF-alpha) enhances enterocyte proliferation and stimulates intestinal adaptation after massive bowel resection. In the present study, we evaluated the effects of TGF-alpha on enterocyte turnover and correlated it with epidermal-growth factor (EGF) receptor expression along the villus-crypt axis in a rat model of short bowel syndrome (SBS). Male rats were divided into three groups, sham rats underwent bowel transection (group A); SBS rats underwent a 75% bowel resection (group B); and SBS/TGF-alpha rats underwent bowel resection and were treated with TGF-alpha (75 microg/kg) (group C) from the seventh postoperative day. Parameters of intestinal adaptation, enterocyte proliferation and apoptosis were determined on day 15. Villus tips, lateral villi and crypts were separated using laser capture microdissection. EGF receptor expression for each compartment was assessed by quantitative real-time PCR (Taqman). Statistical analysis was performed using one-way ANOVA test, with P < 0.05 considered statistically significant. Treatment with TGF-alpha resulted in a significant increase in all parameters of intestinal adaptation. EGF receptor expression in crypts significantly increased in SBS rats (vs sham rats) (0.035 +/- 0.013 vs 0.010 +/- 0.002 Log ng Total RNA/18 s) and was accompanied by a significant increase in enterocyte proliferation (169 +/- 8 vs 138 +/- 5 BrdU positive cells/per 10 crypts, P < 0.05) and decreased apoptosis following TGF-alpha administration (group C). A significant decrease in EGF receptor expression at the tip of the villus (0.005 +/- 0.002 vs 0.029 +/- 0.014 Log ng Total RNA/18 s) and in the lateral villus (0.003 +/- 0.001 vs 0.028 +/- 0.006 Log ng Total RNA/18 s) in SBS (group B) rats (vs sham, group A) was accompanied by increased cell apoptosis in these compartments following treatment with TGF-alpha (group C). In a rat model of SBS, TGF-alpha increased enterocyte proliferation and stimulated intestinal adaptation. The effect of TGF-alpha on enterocyte turnover is correlated with EGF receptor expression along the villus-crypt axis.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Responsiveness of intestinal epithelial cell turnover to TGF-α after bowel resection in a rat is correlated with EGF receptor expression along the villus–crypt axis

et al. 2007

View full text Add to dashboard Cite

show abstract

“…For ovarian cancer cell lines treated with EGF, the nuclear translocation of β-catenin and increased migration capacity have also been reported in a recent study (32). The nuclear translocation of β-catenin was also observed in two colorectal adenocarcinoma cell lines treated with EGF (22). various studies have described that growth factors can regulate the cell content and localization of different types of claudins, but the machinery of this regulation remains unknown.…”

Section: Discussionmentioning

confidence: 68%

“…It has been demonstrated that the EGFR and Wnt/β-catenin pathways might interact in the same way to modulate these events as EGFR activates various downstream kinases, which could modulate the phosphorylation status of GSK3-β and, consequently, activate the Wnt/β-catenin pathway (18)(19)(20). However, there are still controversies concerning this issue as certain authors did not find a relation between these two pathways in events related to cancer progression (21,22).…”

Section: Introductionmentioning

confidence: 99%

Lithium reduces tumorigenic potential in response to EGF signaling in human colorectal cancer cells

Vidal

Araújo²,

Cruz³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. Lithium is a specific inhibitor of GSK3-β, and hence, an activator of the Wnt/β-catenin pathway, whereas the epidermal growth factor (EGF) has been linked to malignant transformation in epithelial cancer cells. Both pathways are aberrantly activated in most colorectal cancers (CRCs). However, the relationship between them in modulating events related to the progression of this cancer type remains to be defined. In this study, we investigated whether the Wnt/β-catenin and EGFR pathways converge to modulate the malignant potential of CRC. We used Caco-2 cells, a well-established model used to study CRC, and treatments with lithium chloride, as a modulator of the Wnt/β-catenin pathway, and with EGF as an inducer of EGFR signaling. We found that both agents altered the subcellular distribution of claudin-1 and β-catenin, two important proteins of the apical junctional complex, but not their abundance in the cell. Nuclear stabilization of β-catenin, a marker of Wnt pathway activation, was observed after treatment with both compounds. However, lithium, but not EGF, inhibited GSK3-β, indicating that these agents modulate this enzyme in a differential fashion. Furthermore, EGF treatment increased the proliferative and migratory capacity but did not alter the colony formation potential of these cells. Surprisingly, lithium, known to activate the Wnt/β-catenin pathway, inhibited the increased proliferation by arresting cells in the G 2 /M phase as well as the cell migration promoted by EGF, as demonstrated by the combined treatment with these agents. Lithium treatment alone reduced the cell colony formation. Thus, our findings suggest that lithium plays an important role in regulating cellular events related to tumor progression in CRC.

show abstract

“…In numerous animal studies, we have shown that HGF can enhance absorption of carbohydrates and protein beyond that which occurs with the normal adaptive process following a major loss of the small intestine [5][6][7]. Epidermal growth factor has also been shown to enhance intestinal adaptation in SBS models, measured by longer villi, deeper crypts, and augmented enterocyte proliferation [8,9]. Thus, there would appear to be a significant potential clinical application for HGF and EGF in the management of patients with SBS to diminish or eliminate the need for TPN supplementation.…”

mentioning

confidence: 99%

Modulation of the inflammatory response and apoptosis using epidermal growth factor and hepatocyte growth factor in a liver injury model: a potential approach to the management and treatment of cholestatic liver disease

Thatch¹,

Schwartz²,

Yoo³

et al. 2008

Journal of Pediatric Surgery

View full text Add to dashboard Cite

Epidermal growth factor receptor-directed enterocyte proliferation does not induce Wnt pathway transcription

Cited by 8 publications

References 27 publications

Responsiveness of intestinal epithelial cell turnover to TGF-α after bowel resection in a rat is correlated with EGF receptor expression along the villus–crypt axis

Responsiveness of intestinal epithelial cell turnover to TGF-α after bowel resection in a rat is correlated with EGF receptor expression along the villus–crypt axis

Lithium reduces tumorigenic potential in response to EGF signaling in human colorectal cancer cells

Modulation of the inflammatory response and apoptosis using epidermal growth factor and hepatocyte growth factor in a liver injury model: a potential approach to the management and treatment of cholestatic liver disease

Contact Info

Product

Resources

About