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Natriuretic peptide receptor a as a novel anticancer target.
- Source :
-
Cancer research [Cancer Res] 2008 Jan 01; Vol. 68 (1), pp. 249-56. - Publication Year :
- 2008
-
Abstract
- The receptor for atrial natriuretic peptide (ANP), natriuretic peptide receptor A (NPRA), is expressed in cancer cells, and natriuretic peptides have been implicated in cancers. However, the direct role of NPRA signaling in tumorigenesis remains elusive. Here, we report that NPRA expression and signaling is important for tumor growth. NPRA-deficient mice showed significantly reduced antigen-induced pulmonary inflammation. NPRA deficiency also substantially protected C57BL/6 mice from lung, skin, and ovarian cancers. Furthermore, a nanoparticle-formulated interfering RNA for NPRA attenuated B16 melanoma tumors in mice. Ectopic expression of a plasmid encoding NP73-102, the NH(2)-terminal peptide of the ANP prohormone, which down-regulates NPRA expression, also suppressed lung metastasis of A549 cells in nude mice and tumorigenesis of Line 1 cells in immunocompetent BALB/c mice. The antitumor activity of NP73-102 was in part attributed to apoptosis of tumor cells. Western blot and immunohistochemistry staining indicated that the transcription factor, nuclear factor-kappaB, was inactivated, whereas the level of tumor suppressor retinoblastoma protein was up-regulated in the lungs of NPRA-deficient mice. Furthermore, expression of vascular endothelial growth factor was down-regulated in the lungs of NPRA-deficient mice compared with that in wild-type mice. These results suggest that NPRA is involved in tumor angiogenesis and represents a new target for cancer therapy.
- Subjects :
- Adenocarcinoma genetics
Adenocarcinoma pathology
Animals
Apoptosis
Cell Transformation, Neoplastic genetics
Female
Guanylate Cyclase antagonists & inhibitors
Guanylate Cyclase genetics
Inflammation genetics
Inflammation pathology
Lung Neoplasms genetics
Lung Neoplasms pathology
Mice
Mice, Knockout
Mice, Mutant Strains
NF-kappa B metabolism
Nanoparticles therapeutic use
Neoplasms drug therapy
Neoplasms genetics
Neovascularization, Pathologic drug therapy
Ovarian Neoplasms genetics
RNA Interference
RNA, Small Interfering genetics
Receptors, Atrial Natriuretic Factor antagonists & inhibitors
Receptors, Atrial Natriuretic Factor genetics
Retinoblastoma Protein metabolism
Skin Neoplasms genetics
Vascular Endothelial Growth Factor A antagonists & inhibitors
Vascular Endothelial Growth Factor A metabolism
Guanylate Cyclase physiology
Neoplasms blood supply
Neovascularization, Pathologic genetics
Receptors, Atrial Natriuretic Factor physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 68
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 18172317
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-07-3086