Tohoku J. Exp. Med., 2009, 217(2)

Decreased Expression of Angiotensin-Converting Enzyme 2 in Pancreatic Ductal Adenocarcinoma Is Associated with Tumor Progression

LIN ZHOU,¹ RUIFENG ZHANG,² WEIYAN YAO,¹ JIANCHENG WANG,³ AIHUA QIAN,¹ MINMIN QIAO,¹ YONGPING ZHANG¹ and YAOZONG YUAN¹

¹Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
²Respiratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
³General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

Angiotensin II (ANG II), the biologically active peptide of the renin-angiotensin system (RAS), is generated by angiotensin-converting enzyme (ACE) and is a regulator of cardiovascular homeostasis. Recently, there has been increasing evidence that ANG II is involved in the regulation of cell proliferation and migration, as well as angiogenesis via the ANG II-type 1 receptor (AT1R). These findings suggest that the ACE-ANG II-AT1R pathway is related to cancer biology. Previous reports have shown that ACE is preferentially expressed in pancreatic ductal adenocarcinoma (PDAC) tissues. Recently a homologue of ACE, angiotensin-converting enzyme 2 (ACE2), was reported to counterbalance the function of ACE, but the expression and role of ACE2 in PDAC are still unclear. In the present study, we analyzed the expression of ACE2 in invasive human PDAC and surrounding non-malignant tissues by Western blot analysis and immunohistochemistry. The ANG II concentration in homogenates of pancreatic tissues was measured with ELISA, and ACE2 protein was detected by Western blot analysis in BxPC3 and SW1990 human pancreatic ductal cancer cells. We have shown for the first time that the expression of ACE2 is decreased in PDAC tissues, in which ANG II was accumulated. Treatment of BxPC3 and SW1990 cells with ANG II decreased the expression of ACE2. Therefore, ANG II may contribute to the down-regulation of ACE2. Moreover, reduction of ACE2 expression by RNA interference promoted the proliferation of cultured pancreatic cancer cells. These findings suggest that ACE2 may have clinical potential as a novel molecular target for the treatment of PDAC.

keywords —— angiotensin-converting enzyme 2; pancreatic ductal adenocarcinoma; angiotensin II; proliferation; angiotensin converting enzyme.

© 2009 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2009, 217, 123-131

Correspondence: Dr. Yaozong Yuan. Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.

e-mail: yyz28@medmail.com.cn