Renin‐angiotensin system is an important factor in hormone refractory prostate cancer

Uemura, Hiroji; Hasumi, Hisashi; Ishiguro, Hitoshi; Teranishi, Jun‐ichi; Miyoshi, Yasuhide; Kubota, Yoshinobu

doi:10.1002/pros.20407

Cited by 57 publications

(44 citation statements)

References 44 publications

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“…Human vascular smooth muscle cells express androgen receptors 31 and would be anticipated to respond to androgen. In addition, incubation of androgen-dependent human prostate cancer cells with DHT increased AT1 receptor mRNA and protein, 32 supporting androgen regulation of human AT1 receptors. However, it is unclear whether human aortic smooth muscle cells expressed along the length of the aorta respond differentially to androgen to increase AT1 receptor expression.…”

Section: Discussionmentioning

confidence: 71%

Androgen Increases AT1a Receptor Expression in Abdominal Aortas to Promote Angiotensin II–Induced AAAs in Apolipoprotein E–Deficient Mice

Henriques

Zhang

Yiannikouris

et al. 2008

ATVB

100

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Objective-Castration of male apolipoprotein E-deficient (apoE Ϫ/Ϫ ) mice reduces angiotensin II (Ang II)-induced abdominal aorta aneurysms (AAAs) to that of female mice. The purpose of this study was to determine whether this reduction is attributable to androgen-mediated regulation of aortic Ang II type 1A receptors (AT1aR). Methods and Results-AT1aR mRNA abundance in the AAA-prone region of abdominal aortas was 8-fold greater compared to thoracic aortas of male but not female mice. AT1aR mRNA abundance decreased after castration in abdominal but not thoracic aortas of male mice. Dihydrotestosterone (DHT, 0.16 mg/d) administration to castrated male mice restored AT1aR mRNA abundance in abdominal aortas but had no effect in thoracic aortas. DHT also increased AT1aR mRNA abundance in abdominal aortas from female mice. Castrated male or female apoE Ϫ/Ϫ mice were administered DHT during infusion of saline or Ang II (1000 ng/kg/min for 28 days). DHT administration did not alter serum cholesterol concentrations, lipoprotein distributions, or atherosclerotic lesion areas in either male or female mice. However, administration of DHT increased AAA incidence in male (27% placebo versus 75% DHT) and female mice (28% placebo versus 64% DHT). Key Words: angiotensin Ⅲ aneurysms Ⅲ androgen Ⅲ atherosclerosis Ⅲ sex hormones A bdominal aortic aneurysms (AAAs) account for 2% of all deaths and are the tenth most common cause of mortality. 1 The incidence and severity of abdominal aortic dilations are greater in males than females. 2,3 Male gender has been consistently identified as a nonmodifiable risk factor for AAA. However, the role of androgens as mediators of gender differences in AAA has not been investigated extensively. Conclusions-AndrogenGender differences also impact AAA formation in experimental models of this disease. In aortic dilation promoted by transient intraluminal elastase infusion, male rats had larger and more frequent AAAs than females. 4 Chronic infusion of angiotensin II (Ang II) into hyperlipidemic mice resulted in AAA formation at a higher incidence in male compared to female mice. [5][6][7][8] In agreement with a potential protection of female gender, estradiol administration to male apolipoprotein E (apoE)-deficient mice reduced Ang II-induced AAA formation. 9 However, ovariectomy of apoE Ϫ/Ϫ mice did not significantly influence AAA formation, suggesting that endogenous ovarian hormones are not primary mediators of gender differences in Ang II-induced AAAs. 8 In contrast, removal of male sex hormones by orchiectomy of apoE Ϫ/Ϫ mice significantly reduced the incidence of Ang II-induced AAAs to that observed in female mice. 8 These data potentially implicate androgen as a primary mediator of gender differences in Ang II-induced AAAs; however, mechanisms of androgen to promote AAA formation are unknown.Androgen has been reported to increase the expression of each component of the renin-angiotensin system (RAS), including angiotensinogen, renin, ACE, and AT1 receptors. 10 Previous studies in our laboratory...

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Section: Discussionmentioning

confidence: 71%

Androgen Increases AT1a Receptor Expression in Abdominal Aortas to Promote Angiotensin II–Induced AAAs in Apolipoprotein E–Deficient Mice

Henriques

Zhang

Yiannikouris

et al. 2008

ATVB

100

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“…Thus, there may be a potential beneficial role of AT2R in cancer, and this idea is supported by data that indicate that pheochromocytoma growth is inhibited by AT2R activation (19). With regard to the prostate, there is clear evidence of a tissue-based renin-angiotensin system within this gland and studies to date indicate beneficial actions of blocking AT1R and activating AT2R (15,(20)(21)(22)(23). For example, AT1R inhibitors decrease the growth of some prostate cancer cell lines and delay the development of prostate cancer, whereas AT2R inhibitors are present and have the ability to inhibit epidermal growth factor-induced prostate cancer cell growth in LNCaP and fast-growing androgen-independent PC3 cell lines (24).…”

Section: Introductionmentioning

confidence: 92%

Angiotensin type 2 receptor–mediated apoptosis of human prostate cancer cells

et al. 2009

Molecular Cancer Therapeutics

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Angiotensin II (Ang II) type 1 receptor blocking drugs have been shown to inhibit the growth of prostate cancer cells and delay the development of prostate cancer. Functional Ang II type 2 receptors (AT2R) are present in these cells and inhibit growth induced by epidermal growth factor. The present studies report apoptosis of prostate cancer cells induced by AT2R overexpression. A recombinant adenoviral vector expressing AT2R (Ad-G-AT2R-EGFP) was transduced into prostate cancer cells, including androgen-independent (DU145 and PC3) and androgen-dependent cell lines (LNCaP). Following AT2R transduction, apoptosis was analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining and caspase-3 activity assays. The results indicate that increased expression of AT2R alone induced apoptosis in the prostate cancer lines, an effect that did not require Ang II. AT2R overexpression in DU145 cells induced inhibition of proliferation, a significant reduction of S-phase cells, and an enrichment of G 1 -phase cells. The data also indicate that overexpression of AT2R led to apoptosis via an extrinsic cell death signaling pathway that is dependent on activation of p38 mitogen-activated protein kinase, caspase-8, and caspase-3. Finally, the apoptosis induced by AT2R over-

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“…The RAS is deregulated in several cancers and can influence several aspects of tumor growth. [1][2][3][4][5] Enzymatic action by the angiotensin converting enzyme (ACE) yields the principal effector peptide of the RAS, Angiotensin II (ANG II). ANG II mediates proliferative, angiogenic, and inflammatory effects through the angiotensin type I receptor (AT1R).…”

Section: Introductionmentioning

confidence: 99%

The renin angiotensin system regulates Kupffer cells in colorectal liver metastases

Wen

Ager

Neo

et al. 2013

Cancer Biology & Therapy

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Renin‐angiotensin system is an important factor in hormone refractory prostate cancer

Abstract: The present data suggest that prostatic RAS is overexpressed in HRPC tissue, and expression of its components is influenced by several kinds of hormonal stimulation.

Cited by 57 publications

References 44 publications

Androgen Increases AT1a Receptor Expression in Abdominal Aortas to Promote Angiotensin II–Induced AAAs in Apolipoprotein E–Deficient Mice

Androgen Increases AT1a Receptor Expression in Abdominal Aortas to Promote Angiotensin II–Induced AAAs in Apolipoprotein E–Deficient Mice

Angiotensin type 2 receptor–mediated apoptosis of human prostate cancer cells

The renin angiotensin system regulates Kupffer cells in colorectal liver metastases

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