Association between AT1 and AT2 angiotensin II receptor expression with cell proliferation and angiogenesis in operable breast cancer

Abstract

Angiotensin II (ANGII) has been associated with vascular proliferation in tumor and non-tumor models through its receptors AT1 and AT2. Our objective was to determine AT1 and AT2 receptor expression in operable breast cancer and its association with tumor grade, vascular density, and cellular proliferation. Seventy-seven surgically malignant breast tumors with no distant metastasis were included, and 7 benign lesions were used as controls. AT1 and AT2 receptor expression was determined by RT-PCR and immunohistochemistry (IHC) in 68 out of the 77 malignant lesions and in the 7 benign lesions. AT1 and AT2 receptor expression was detected in 35.3 and 25 % of cases, in both RT-PCR and IHC. Tumors that express AT1 showed an increase in T3 stage (92.3 vs. 7.7 % p < 0.001), mitotic index (4 ± 1 vs 2 ± 1, p = 0.05), vascular density (15 ± 3 vs 8 ± 5, p = 0.05), and cellular proliferation (85 ± 18 vs 55 ± 10, p = 0.01) versus AT1-negative lesions. Non-differences between clinical-pathologic variables and AT2 expression were found. AT1 receptor expression was associated to enhance angiogenesis and cellular proliferation rate, but no relationship with AT2 was found. ANGII and its peptides might play a role in the development and pathophysiology of breast cancer, and this could be valuable in the in the development of targeted therapies.

Angiotensin II Enhances Proliferation and Inflammation through AT1/PKC/NF-κB Signaling Pathway in Hepatocellular Carcinoma Cells

“…Recent study reported that AT1 expression was associated with enhance angiogenesis and cellular proliferation rate, but no relationship was found with AT2 in breast cancer [8]. Consistent with these results, in the present study, we found increased expression of AT1 and decreased expression of AT2 in HCC cells and tissues.…”

Ki67 Changes Identify Worse Outcomes in Residual Breast Cancer Tumors After Neoadjuvant Chemotherapy

“…Since 1999, it has been reported that a decrease in the cell proliferation fraction has a predictive value with respect to the recurrence rate . Ki67 has been used as a marker of such proliferation.…”

Association between Angiotensin-Converting Enzyme Inhibitors and Lung Cancer—A Nationwide, Population-Based, Propensity Score-Matched Cohort Study

“…Studies have reported that angiotensin II receptors, AT1 receptors and AT2 receptors are involved in enhancing tissue vascular endothelial growth factor protein levels, angiogenesis and tumor growth [29,30]. In addition, AT1 receptors are abundantly expressed in malignant neoplasms, including various types of lung cancer [31][32][33][34]. Fujita et al revealed that blocking angiotensin II receptors could reduce tumor growth and metastasis [35].…”