Involvement of angiotensin II type 2 receptor (AT2R) signaling in human pancreatic ductal adenocarcinoma (PDAC): a novel AT2R agonist effectively attenuates growth of PDAC grafts in mice

Cancer Biology & Therapy
Susumu IshiguroMasaaki Tamura

Abstract

We have recently discovered the potential involvement of angiotensin II type 2 receptor (AT2R) signaling in pancreatic cancer using AT2R deficient mice. To examine the involvement of AT2R expression in human PDAC, expressions of AT2R as well as the major angiotensin II receptor (type 1 receptor, AT1R) in human PDAC and adjacent normal tissue was evaluated by immunohistochemistry and real time PCR using surgically dissected human PDAC specimens. In immunohistochemical analysis, relatively strong AT1R expression was detected consistently in both normal pancreas and PDAC areas, whereas moderate AT2R expression was detected in 78.5% of PDAC specimens and 100% of normal area of the pancreas. AT1R, but not AT2R, mRNA levels were significantly higher in the PDAC area than in the normal pancreas. AT2R mRNA levels showed a negative correlation trend with overall survival. In cell cultures, treatment with a novel AT2R agonist significantly attenuated both murine and human PDAC cell growth with negligible cytotoxicity in normal epithelial cells. In a mouse study, administrations of the AT2R agonist in tumor surrounding connective tissue markedly attenuated growth of only AT2R expressing PAN02 murine PDAC grafts in syngeneic mice. The AT2R...Continue Reading

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Jun 14, 2017·Medicinal Research Reviews·Mathias HallbergAnders Hallberg
Feb 16, 2020·British Journal of Pharmacology·Krishna SriramPaul A Insel
Jul 22, 2020·Chemistry : a European Journal·Eirinaios I VrettosAndreas G Tzakos
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May 4, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Susumu IshiguroMasaaki Tamura
Apr 3, 2021·Molecular Pharmacology·Arina RanjitAli Aghazadeh-Habashi

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Methods Mentioned

BETA
PCR
transfection
pancreatectomy
protein assay

Software Mentioned

Micro Suite Five

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