Transforming Growth Factor- beta Receptor Type II Deletion Increases the Multiplicity and Growth of K-ras-induced Lung Cancers

Transforming growth factor- beta (TGF- beta ) is a pluripotent regulator of epithelial growth and homeostasis and functions as a tumor suppressor in numerous malignancies. TGF- beta signaling defects are common in many malignancies, including non-small cell lung cancer (NSCLC); however, the mechanisms by which defective TGF- beta signaling promotes lung cancer growth and development are relatively unknown. The authors generated a novel NSCLC mouse model by simultaneously activating oncogenic Kras super( G12D) expression and deleting TGF- beta receptor type II (TGF- beta RII) in airway epithelial cells. Interestingly, these animals develop both thyroid transcription factor-positive adenocarcinomas and K5-positive squamous cell carcinomas. Mechanistically, TGF- beta RII deletion increases the multiplicity and growth of K-ras -- induced lung cancers through mechanisms involving increased proliferation and increased inflammation.