Aminoflavone Inhibits α6-integrin and Growth of Tamoxifen Resistant Breast Cancer

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Basic Sciences

Year

2018

Author dc:creator

• Campbell, Petreena S.

Contributors dc:contributor

• Brantley, Eileen
• Nagaraj, Gayathri
• Soto, Ubaldo
• Wang, Charles
• Zhang, Lubo

• Medical Pharmacology
• Medical Sciences
• Medicinal and Pharmaceutical Chemistry
• Medicine and Health Sciences
• Neoplasms
• flavonoids; Amines; Breast Neoplasms; Breast Cancer
• Tamoxifen Resistant Cells
• Estrogen Receptor Positive

Statement dc:rights

• 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.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/498

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-1499