Aquaporin-1 gene deletion reduces breast tumor growth and lung metastasis in tumor-producing MMTV-PyVT mice

FASEB J. 2014 Mar;28(3):1446-53. doi: 10.1096/fj.13-245621. Epub 2013 Dec 12.


Aquaporin 1 (AQP1) is a plasma membrane water-transporting protein expressed strongly in tumor microvascular endothelia. We previously reported impaired angiogenesis in implanted tumors in AQP1-deficient mice and reduced migration of AQP1-deficient endothelial cells in vitro. Here, we investigated the consequences of AQP1 deficiency in mice that spontaneously develop well-differentiated, luminal-type breast adenomas with lung metastases [mouse mammary tumor virus-driven polyoma virus middle T oncogene (MMTV-PyVT)]. AQP1(+/+) MMTV-PyVT mice developed large breast tumors with total tumor mass 3.5 ± 0.5 g and volume 265 ± 36 mm(3) (SE, 11 mice) at age 98 d. Tumor mass (1.6±0.2 g) and volume (131±15 mm(3), 12 mice) were greatly reduced in AQP1(-/-) MMTV-PyVT mice (P<0.005). CD31 immunofluorescence showed abnormal microvascular anatomy in tumors of AQP1(-/-) MMTV-PyVT mice, with reduced vessel density. HIF-1α expression was increased in tumors in AQP1(-/-) MMTV-PyVT mice. The number of lung metastases (5±1/mouse) was much lower than in AQP1(+/+) MMTV-PyVT mice (31±8/mouse, P<0.005). These results implicate AQP1 as an important determinant of tumor angiogenesis and, hence, as a potential drug target for adjuvant therapy of solid tumors.

Keywords: AQP1; endothelia; water channel.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 1 / genetics*
  • Breast Neoplasms / blood supply
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Gene Deletion*
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / genetics
  • Lung Neoplasms / secondary*
  • Mice
  • Mice, Knockout
  • Neovascularization, Pathologic / genetics


  • Aquaporin 1