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

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Tumor Biology

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.

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The authors have no relevant financial involvement with any organization with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

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Authors and Affiliations

  1. Medical Oncology Department, Instituto Nacional de Cancerología, San Fernando # 22, Sección XVI, Tlalpan, 14080, México, D.F., Mexico

    Oscar Arrieta

  2. Experimental Oncology Laboratory, Instituto Nacional de Cancerología, Mexico City, Mexico

    Oscar Arrieta, Norma Hernández-Pedro & Geraldine Villanueva-Rodríguez

  3. Universidad Nacional Autónoma de México, Mexico City, Mexico

    Oscar Arrieta

  4. Unit of Biomedical Cancer Research, Instituto Nacional de Cancerología, Mexico City, Mexico

    Cynthia Villarreal-Garza & Talia Wegman-Ostrosky

  5. Breast Cancer Center, Tecnológico de Monterrey, Monterrey, N.L., Mexico

    Cynthia Villarreal-Garza

  6. Biochemistry Department, Instituto Nacional de Cancerología, Mexico City, Mexico

    Gloria Vizcaíno

  7. Neuroimmunology Unit, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico

    Benjamín Pineda & Patricia Guevara-Salazar

  8. Pathology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

    Armando Gamboa-Domínguez

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Arrieta, O., Villarreal-Garza, C., Vizcaíno, G. et al. Association between AT1 and AT2 angiotensin II receptor expression with cell proliferation and angiogenesis in operable breast cancer. Tumor Biol. 36, 5627–5634 (2015). https://doi.org/10.1007/s13277-015-3235-3

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