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2015 ; 16
(2
): 307-16
Nephropedia Template TP
gab.com Text
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English Wikipedia
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
#MMPMID25756513
Ishiguro S
; Yoshimura K
; Tsunedomi R
; Oka M
; Takao S
; Inui M
; Kawabata A
; Wall T
; Magafa V
; Cordopatis P
; Tzakos AG
; Tamura M
Cancer Biol Ther
2015[]; 16
(2
): 307-16
PMID25756513
show ga
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 agonist treatment
induced apoptosis primarily in tumor cells but not in stromal cells. Taken
together, our findings offer clinical and preclinical evidence for the
involvement of AT2R signaling in PDAC development and pinpoint that the novel
AT2R agonist could serve as an effective therapeutic for PDAC treatment.