부산대학교 도서관

Acquired resistance to TGFβ is a key step in the early stages of tumorigenesis. Mutations in TGFb signaling components are rare, and little is known about the development of resistance in breast cancer. On the other hand, an activated Notch pathway is known to play a substantial role in promoting breast cancer development. Here, we present evidence of cross talk between these two pathways through HEYL. HEYL, a basic helix--loop--helix transcription factor and a direct target of Notch signaling, is specifically over expressed in breast cancer. HEYL represses TGFβ activity by binding to TGFβ-activated Smads. HeyL-/- mice have defective mammary gland development with fewer terminal end buds. On the other hand, HeyL transgenic mice show accelerated mammary gland epithelial proliferation and 24% of multiparous mice develop mammary gland cancer. Therefore, repression of TGFβ signaling by Notch acting through HEYL may promote initiation of breast cancer. [ABSTRACT FROM AUTHOR]