Abstract
Triple negative breast cancer (TNBC) patients do not benefit from directed therapy because these tumors do not express targetable molecules; such as, hormone or growth factor receptors (ER, PR and HER2). This subtype represents 15-20% of all breast cancer cases diagnosed in women in the United States. Higher incidence of TNBC affects, particularly, young African American women compared with other women. Clinically, TNBC patients often present an advanced stage disease. These tumors exhibit an increased inflammatory signal and an aggressive phenotype that leads to an increased frequency of metastasis. These patients have a poor survival outcome. Coincidentally, expression of the amplified in breast cancer 1 (AIB1) oncogene has also been reported in higher grade, inflammatory and invasive breast cancer. AIB1 is a nuclear coactivator that regulates transcription of several genes through hormone and/or growth factor signaling. Here we demonstrate that cell lines derived from tumors in African American women representing different TNBC subtypes have varying degree of sensitive to AIB1 shRNA by lentiviral infection. AIB1 knockdown has a considerable effect on viability of all the TNBC subtypes; however, we observed the presence of a small fraction of cells that proliferate independent of AIB1. Interestingly, these cells that retain the AIB1 knockdown following sub-culture for 3-4 passages are comparable to the initial TNBC cells as regards to cell cycle and apoptosis. Intriguingly, these TNBC cells that proliferate independent of AIB1 show increase in the percentage of cells expressing CD44+/CD24- cell surface markers indicating a selection of tumor initiating cells. Concomitantly, there is a decrease in the percentage of CD44-/CD24- cells suggesting that AIB1 may regulate tumor initiating cell differentiation upon external stresses such as those caused by chemotherapeutic agents during treatment. We will further study the chemo sensitivity of TNBC cells resistant to AIB1 loss and assess whether these cells represent a model of cancer cell dormancy associated to recurrence in TNBC patients.
Citation Format: Francisco R. Saenz, Anna T. Riegel. Elucidating the role of AIB1 in triple-negative breast cancer cell lines. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C63.
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