Approximately 40% of estrogen receptor positive (ER+) breast cancer patients develop resistance to standard of care agent tamoxifen, while ER negative (ER-) breast cancer patients are intrinsically resistant to tamoxifen. Resistance often promotes metastasis, recurrence and death. Tumor-initiating cells (TICs) represent key contributors to resistance and adhesion protein α6-integrin is a putative TIC biomarker. Investigational agent Aminoflavone (AF) demonstrates efficacy against breast cancer cells irrespective of ER status. Interestingly, we found tamoxifen resistant (TamR) cells and tumors exhibited elevated α6-integrin expression in comparison to their tamoxifen sensitive counterparts. AF effectively disrupted mammospheres enriched for TICs and reduced α6-integrin levels in tamoxifen sensitive and TamR cells. AF further inhibited α6-integrin’s pro-cancer signaling in TamR cells. Additionally, AF altered the miRNA expression profile of tamoxifen sensitive and TamR mammosphere-derived cells. Our data suggest that AF inhibits α6-integrin signaling and alters the expression of specific miRNAs to reduce TIC capacity and counteract tamoxifen resistance.
School of Medicine
Doctor of Philosophy (PhD)
Year Degree Awarded
Date (Title Page)
Library of Congress/MESH Subject Headings
flavonoids; Amines; Breast Neoplasms; Breast Cancer
Subject - Local
Tamoxifen Resistant Cells; Estrogen Receptor Positive
Loma Linda University Libraries
This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.
Campbell, Petreena S., "Aminoflavone Inhibits α6-integrin and Growth of Tamoxifen Resistant Breast Cancer" (2018). Loma Linda University Electronic Theses, Dissertations & Projects. 498.
Loma Linda University Electronic Theses and Dissertations
Loma Linda University. Del E. Webb Memorial Library. University Archives