Induction of ErbB-3 Expression by α6β4 Integrin Contributes to Tamoxifen Resistance in ERβ1-Negative Breast Carcinomas

PLOS ONE, February 2008

18270579

Valentina Folgiero, Paolo Avetrani, Giulia Bon, Selene E. Di Carlo, Alessandra Fabi, Cecilia Nisticò, Patrizia Vici, Elisa Melucci, Simonetta Buglioni, Letizia Perracchio, Isabella Sperduti, Laura Rosanò, Ada Sacchi, Marcella Mottolese, Rita Falcioni

Tamoxifen is still the most widely used drug in hormone therapy for the treatment of breast cancer. Its benefits in adjuvant treatment are well documented in controlled and randomized clinical studies, which have demonstrated an increase in disease-free intervals of patients with positive hormonal receptors. However, the mechanisms involved in endocrine resistance are not clear. Laboratory and clinical data now indicate that bi-directional molecular cross-talk between nuclear or membrane ER and growth factor receptor pathways may be involved in endocrine resistance. We recently found a functional interaction between alpha6beta4 integrin and ErbB-3 receptor to maintain the PI3K/Akt survival pathway of mammary tumour cells. We sought to improve understanding of this process in order to provide the involvement of both receptors insight into mechanism of Tamoxifen resistance.