Mechanisms through which Rat Mammary Gland Carcinogenesis is Preferentially Initiated by H-Ras over K-Ras Signaling Pathways
Abstract
This research distinguishes mechanisms through which activated Ras initiates rat mammary gland carcinogenesis. Experiments expressing H-Ras and K-Ras chimeric proteins in mammary gland (Aim lA) investigate hypothesis one: differential rat mammary gland carcinogenesis results from differences in the last 20 amino acids of 11-Ras and K-Ras K-Ras with an H-Ras c-terminus seems as tumorgenic as H- Ras, supporting hypothesis one: however, 11-Ras with an K-Ras c-terminus also seems as tumorgenic as H-Ras,suggesting a unique characteristic of intact K-Ras reduces mammary carcinogenesis. - Expression of Raf-Caax (Aim 1B), does not cause tumors, suggesting hypothesis two: no individual Ras effector will initiate transformation, rather multiple effectors must synergise. Expressing Ras effector loop mutants (ELM), (Aim 2A), weakens hypothesis two. Each Ras ELM (G37 activates RalGDS, E38 activates Raf, and C40 activates Pl3K), individually causes tumors. E38-Ras, which activates Raf, is tumorgenic-yet Raf-Caax is not. These results suggested E38 Ras is activating an additional effector pathway(s), or that Raf-Caax is defective for in situ tumor formation. Early result tumor formation from a-terminus truncated Raf (deltaRaf) shows Raf-Caax is defective, and eliminates hypothesis two.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA396847
Entities
People
- Daniel Mcfarlin
Organizations
- University of Wisconsin–Madison