Background: Epidermal growth factor receptor (EGFR) stimulation enhances intestinal adaptation after massive small bowel resection (SBR), measured by taller villi, deeper crypts, and augmented enterocyte proliferation. Min mice with constitutively active beta-catenin signaling demonstrate enhanced villus growth after SBR, suggesting a role for the Wnt pathway during adaptation. Because there is crosstalk between EGFR signaling and the Wnt pathway, we hypothesized that beta-catenin is modulated by EGFR-induced enterocyte proliferation.
Methods: Rat intestinal epithelial cells were stimulated with EGF and cytoplasmic to nuclear trafficking of beta-catenin was measured. Beta-catenin-directed transcription was also tested via transfection with a TOP/FOP luciferase reporter. Downstream transcriptional target expression was measured in murine intestine after SBR.
Results: Epidermal growth factor-treated rat intestinal epithelial cells exhibited increased proliferation compared to serum-deficient cells in the face of no detectable accumulation of nuclear beta-catenin. The luciferase assay results showed minimal transcription activity in response to EGF. In vivo experiments revealed no significant difference in expression of beta-catenin targeted genes in crypt enterocytes after SBR.
Conclusions: The mechanism for EGFR-induced proliferation of enterocytes does not appear to involve a transcriptional role for beta-catenin. The effects of EGFR signaling on beta-catenin-mediated cell adhesion remain to be investigated.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jpedsurg.2007.01.032 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Omega-3 fatty acids: molecular weapons against chemoresistance in breast cancer.
Cell Mol Biol Lett
January 2025
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata Di Rende, 87036, Cosenza, Italy.
Breast cancer is the most commonly diagnosed type of cancer and the leading cause of cancer-related death in women worldwide. Highly targeted therapies have been developed for different subtypes of breast cancer, including hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, triple-negative breast cancer (TNBC) and metastatic breast cancer disease are primarily treated with chemotherapy, which improves disease-free and overall survival, but does not offer a curative solution for these aggressive forms of breast cancer.
View Article and Find Full Text PDFA forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.
Dev Cell
January 2025
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:
Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.
View Article and Find Full Text PDFA promising future for breast cancer therapy with hydroxamic acid-based histone deacetylase inhibitors.
Bioorg Chem
January 2025
Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India. Electronic address:
Histone deacetylases (HDACs) play a critical role in chromatin remodelling and modulating the activity of various histone proteins. Aberrant HDAC functions has been related to the progression of breast cancer (BC), making HDAC inhibitors (HDACi) promising small-molecule therapeutics for its treatment. Hydroxamic acid (HA) is a significant pharmacophore due to its strong metal-chelating ability, HDAC inhibition properties, MMP inhibition abilities, and more.
View Article and Find Full Text PDFPopulation pharmacokinetics of erlotinib in patients with non-small cell lung cancer (NSCLC): A model-based meta-analysis.
Comput Biol Med
January 2025
Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; Department of Pharmaceutical Medicine and Regulatory Science, Yonsei University, Incheon, Republic of Korea; Graduate Program of Industrial Pharmaceutical Science, Yonsei University, Incheon, Republic of Korea; Department of Integrative Biotechnology, Yonsei University, Incheon, Republic of Korea. Electronic address:
Background: Erlotinib is a potent first-generation epidermal growth factor receptor tyrosine kinase inhibitor. Due to its proximity to the upper limit of tolerability, dose adjustments are often necessary to manage potential adverse reactions resulting from its pharmacokinetic (PK) variability.
Methods: Population PK studies of erlotinib were identified using PubMed databases.
Epiregulin ameliorates ovariectomy-induced bone loss through orchestrating the differentiation of osteoblasts and osteoclasts.
J Bone Miner Res
January 2025
NHC Key Lab of Hormones and Development, Tianjin Key Lab of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China.
Epiregulin plays a role in a range of biological activities including malignancies. This study aims to investigate the potential contribution of epiregulin to bone cell differentiation and bone homeostasis. The data showed that epiregulin expression was upregulated during osteogenesis but downregulated during adipogenesis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!