The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis

Koichi Hamada, Takehiko Sasaki, Pandelakis A. Koni, Miyuki Natsui, Hiroyuki Kishimoto, Junko Sasaki, Nobuyuki Yajima, Yasuo Horie, Go Hasegawa, Makoto Naito, Jun Ichi Miyazaki, Toshio Suda, Hiroshi Itoh, Kazuwa Nakao, Wah Mak Tak, Toru Nakano, Akira Suzuki

研究成果: Article査読

236 被引用数 (Scopus)


PTEN is an important tumor suppressor gene. Hereditary mutation of PTEN causes tumor-susceptibility diseases such as Cowden disease. We used the Cre-loxP system to generate an endothelial cell-specific mutation of Pten (Tie2CrePten) in mice. Tie2CrePtenflox/+ mice displayed enhanced tumorigenesis due to an increase in angiogenesis driven by vascular growth factors. This effect was partially dependent on the PI3K subunits p85α and p110γ. In vitro, Tie2CrePtenflox/+ endothelial cells showed enhanced proliferation/migration. Tie2CrePtenflox/flox mice died before embryonic day 11.5 (E11.5) due to bleeding and cardiac failure caused by impaired recruitment of pericytes and vascular smooth muscle cells to blood vessels, and of cardiomyocytes to the endocardium. These phenotypes depend strongly on p110γ rather than on p85α and were associated with decreased expression of Ang-1, VCAM-1, connexin 40, and ephrinB2 but increased expression of Ang-2, VEGF-A, VEGFR1, and VEGFR2. Pten is thus indispensable for normal cardiovascular morphogenesis and post-natal angiogenesis, including tumor angiogenesis.

ジャーナルGenes and Development
出版ステータスPublished - 2005 9月 1

ASJC Scopus subject areas

  • 遺伝学
  • 発生生物学


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