Kinetics of v-src-induced epithelial-mesenchymal transition in developing glandular stomach

Area of Science:

• Developmental Biology
• Cell Biology
• Oncogenesis

Background:

• The role of oncogenes in primary epithelial cells remains poorly understood.
• Investigating oncogene function requires specific gene transfer methods into distinct cell types.

Purpose of the Study:

• To elucidate the function of oncogenes in primary epithelial cells using a novel organ culture system.
• To investigate the molecular mechanisms underlying oncogene-induced epithelial-mesenchymal transition (EMT).

Main Methods:

• Utilized recombination organ cultures of developing avian glandular stomach (proventriculus).
• Employed retroviral and electroporation techniques for stable and transient gene transfer of oncogenes.
• Analyzed gene expression changes (Sonic hedgehog, E-cadherin, collagen I, fibronectin) and cellular behaviors (migration, apoptosis).

Main Results:

• Expression of v-src in epithelial cells induced budding and migration into the mesenchyme.
• Transient v-src or MEK activation led to Sonic hedgehog downregulation and E-cadherin loss, implicating MAP kinase signaling.
• Continuous v-src expression promoted acquisition of mesenchymal markers and established epithelial-mesenchymal transition (EMT).

Conclusions:

• Oncogene expression can reprogram epithelial cells, driving migration and EMT.
• The MAP kinase pathway plays a critical role in mediating oncogene-induced cellular changes.
• These findings provide insights into the distinct oncogenic outcomes of Rous sarcoma virus (RSV), explaining sarcoma formation.