RESEARCH ARTICLE Association between AT1 and AT2 angiotensin II receptor expression with cell proliferation and angiogenesis in operable breast cancer Oscar Arrieta & Cynthia Villarreal-Garza & Gloria Vizcaíno & Benjamín Pineda & Norma Hernández-Pedro & Patricia Guevara-Salazar & Talia Wegman-Ostrosky & Geraldine Villanueva-Rodríguez & Armando Gamboa-Domínguez Received: 4 November 2014 /Accepted: 6 February 2015 # International Society of Oncology and BioMarkers (ISOBM) 2015 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 immunohisto- chemistry (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 prolif- eration (85±18 vs 55±10, p =0.01) versus AT1-negative le- sions. 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 pathophys- iology of breast cancer, and this could be valuable in the in the development of targeted therapies. Keywords ATI . ATII . Angiotensin II . Breast cancer . Angiogenesis . AT1 blockers Introduction Worldwide, breast cancer (BC) is the leading cause of cancer- related deaths in women [1]. The prognosis depends on mul- tiple factors, such as stage and age at diagnosis, degree of differentiation, cellular proliferation, estrogen, and progester- one receptor positivity and overexpression of HER2/neu [2]. These factors also represent the basis of current therapies to HER2-targeted treatments or adjuvant/palliative hormonal treatment [3–5]. Although advances have been achieved throughout time, BC remains as a public health issue with a high mortality rate. O. Arrieta (*) Medical Oncology Department, Instituto Nacional de Cancerología, San Fernando # 22, Sección XVI, Tlalpan, 14080 México, D.F., Mexico e-mail: ogar@unam.mx O. Arrieta : N. Hernández-Pedro : G. Villanueva-Rodríguez Experimental Oncology Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico O. Arrieta Universidad Nacional Autónoma de México, Mexico City, Mexico C. Villarreal-Garza : T. Wegman-Ostrosky Unit of Biomedical Cancer Research, Instituto Nacional de Cancerología, Mexico City, Mexico C. Villarreal-Garza Breast Cancer Center, Tecnológico de Monterrey, Monterrey, N.L., Mexico G. Vizcaíno Biochemistry Department, Instituto Nacional de Cancerología, Mexico City, Mexico B. Pineda : P. Guevara-Salazar Neuroimmunology Unit, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico A. Gamboa-Domínguez Pathology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico Tumor Biol. DOI 10.1007/s13277-015-3235-3