Retinoic acid reduces migration of human breast cancer cells: role of retinoic acid receptor beta

Breast cancer is the most common malignancy in women and the appearance of distant metastases produces the death in 98% of cases. The retinoic acid receptor b (RARb) is not expressed in 50% of invasive breast carcinoma compared with normal tissue and it has been associated with lymph node metastasis. Our hypothesis is that RARb protein participates in the metastatic process. T47D and MCF7 breast cancer cell lines were used to perform viability assay, immunobloting, migration assays, RNA interference and immunofluorescence. Administration of retinoic acid (RA) in breast cancer cells induced RARb gene expression that was greatest after 72 hrs with a concentration 1 lM. High concentrations of RA increased the expression of RARb causing an inhibition of the 60% in cell migration and significantly decreased the expression of migration-related proteins [moesin, c-Src and focal adhesion kinase (FAK)]. The treatment with RARa and RARc agonists did not affect the cell migration. On the contrary, the addition of the selective retinoid RARb-agonist (BMS453) significantly reduced cell migration comparable to RA inhibition. When RARb gene silencing was performed, the RA failed to significantly inhibit migration and resulted ineffective to reduce moesin,c-Src and FAK expressions. RARb is necessary to inhibit migration induced by RA in breast cancer cells modulating the expression of proteins involved in cell migration.Fil: Flamini, Marina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Gauna, Gisel Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Sanchez, Angel Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Prognostic implication of HSPA (HSP70) in breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy

Neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to reduce the tumor size before surgery. Unfortunately, resistance to chemotherapy may arise from a variety of mechanisms. The heat shock proteins (HSPs), which are highly expressed in mammary tumor cells, have been implicated in anticancer drug resistance. In spite of the widely described value of HSPs as molecular markers in cancer, their implications in breast tumors treated with anthracycline-based neoadjuvant chemotherapy has been poorly explored. In this study, we have evaluated by immunohistochemistry the expression of HSP27 (HSPB1) and HSP70 (HSPA) in serial biopsies from locally advanced breast cancer patients (n= 60) treated with doxorubicin (DOX) or epirubicin (EPI) based monochemotherapy. The serial biopsies were taken at days 1, 3, 7, 21, and compared with the pre-chemotherapy and the surgical biopsies. After surgery the patients received additional chemotherapy with Cyclophosphamide, Methotrexate and 5-Fluorouracil (CMF). High nuclear HSPB1 and HSPA expressions were found in invasive cells after DOX/EPI administration (P31% of the cells) and cytoplasmic HSPA expressions (>11% of the tumor cells) were associated with better DFS (P=0.0348 and P=0.0118, respectively). We conclude that HSPA expression may be a useful prognostic marker in breast cancer patients treated with neoadjuvant DOX/EPI chemotherapy, indicating the need to change the administered drugs after surgery for overcoming drug resistance.Fil: Nadin, Silvina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Sottile Fleury, Mayra Lis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Montt Guevara, Maria Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Gauna, Gisel Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Daguerre, Pedro. Hospital Luis Lagomaggiore; ArgentinaFil: Leuzzi, Marcela. Hospital Luis Lagomaggiore; ArgentinaFil: Gago, Francisco E.. Universidad Nacional de Cuyo; ArgentinaFil: Ibarra, Jorge. Hospital Luis Lagomaggiore; ArgentinaFil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Vargas Roig, Laura Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin