+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

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



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



Genes and Development 19(17): 2054-2065



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. Tie2CrePten(flox/+) mice displayed enhanced tumorigenesis due to an increase in angiogenesis driven by vascular growth factors. This effect was partially dependent on the PI3K subunits p85alpha and p110gamma. In vitro, Tie2CrePten(flox/+) endothelial cells showed enhanced proliferation/migration. Tie2CrePten(flox/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 p110gamma rather than on p85alpha 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.

(PDF emailed within 0-6 h: $19.90)

Accession: 012631487

Download citation: RISBibTeXText

PMID: 16107612

DOI: 10.1101/gad.1308805


Related references

The Pten/PI3K pathway governs the homeostasis of Valpha14iNKT cells. Blood 109(8): 3316-3324, 2006

The Pten/PI3K pathway governs the homeostasis of V alpha 14iNKT cells. Blood 109(8): 3316-3324, 2007

PI3K/PTEN/AKT signaling regulates prostate tumor angiogenesis. Cellular Signalling 19(12): 2487-2497, 2007

Relations of synovial angiogenesis and PTEN/PI3K/AKT signaling pathway in rats with adjuvant arthritis. Zhongguo Gu Shang 28(1): 71-74, 2015

PTEN regulates angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells. Molecular and Cellular Biochemistry 331(1-2): 161-171, 2010

HIV-1 Tat promotes Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6-induced angiogenesis and tumorigenesis by regulating PI3K/PTEN/AKT/GSK-3β signaling pathway. Plos One 8(1): E53145, 2013

Antitumor effect of a selective COX-2 inhibitor, celecoxib, may be attributed to angiogenesis inhibition through modulating the PTEN/PI3K/Akt/HIF-1 pathway in an H₂₂ murine hepatocarcinoma model. Oncology Reports 31(5): 2252-2260, 2015

PTEN Tumor Suppressor Network in PI3K-Akt Pathway Control. Genes and Cancer 1(12): 1170-1177, 2011

Effect of IGF-1 on PI3K/PTEN signal pathway in vascular smooth muscle cell. Zhongguo Ying Yong Sheng Li Xue Za Zhi 20(3): 259-262, 2012

JQ1 suppresses tumor growth via PTEN/PI3K/AKT pathway in endometrial cancer. Oncotarget 7(41): 66809-66821, 2016

T11TS impedes glioma angiogenesis by inhibiting VEGF signaling and pro-survival PI3K/Akt/eNOS pathway with concomitant upregulation of PTEN in brain endothelial cells. Journal of Neuro-Oncology 113(1): 13-25, 2013

Role of the PTEN/PI3K/VEGF pathway in the development of Kawasaki disease. Experimental and Therapeutic Medicine 11(4): 1318-1322, 2016

Mutation analysis of tumor suppressor gene PTEN in patients with gastric carcinomas and its impact on PI3K/AKT pathway. Oncology Reports 24(1): 89-95, 2010

Crosstalk between Meg3 and miR-1297 regulates growth of testicular germ cell tumor through PTEN/PI3K/AKT pathway. American Journal of Translational Research 8(2): 1091-1099, 2016

PTEN regulation of the proliferation and differentiation of auditory progenitors through the PTEN/PI3K/Akt-signaling pathway in mice. Neuroreport 25(3): 177-183, 2014