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.
","abstract_html":"<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>","abstract_has_math":false,"creators":["Campbell, Petreena S."],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Basic Sciences","degree_department":null,"school":null,"contributors":["Brantley, Eileen","Nagaraj, Gayathri","Soto, Ubaldo","Wang, Charles","Zhang, Lubo"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-08-01T07:00:00Z","date_published":"2018-08-01T07:00:00Z","updated_at":"2026-07-24T02:52:45Z","subjects":["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"],"languages":["English"],"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."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarsrepository.llu.edu/etd/498","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Brantley, Eileen","Nagaraj, Gayathri","Soto, Ubaldo","Wang, Charles","Zhang, Lubo"]},{"key":"dc:creator","label":"Author","values":["Campbell, Petreena S."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Basic Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["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"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:rights","label":"Dc Rights","values":["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."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarsrepository.llu.edu/etd/498"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Aminoflavone Inhibits α6-integrin and Growth of Tamoxifen Resistant Breast Cancer"]}]}],"canonical_facts":{"dc:contributor":["Brantley, Eileen","Nagaraj, Gayathri","Soto, Ubaldo","Wang, Charles","Zhang, Lubo"],"dc:creator":["Campbell, Petreena S."],"dc:description.abstract":["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.
"],"dc:identifier":["https://scholarsrepository.llu.edu/etd/498"],"dc:language":["English"],"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."],"dc:subject":["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"],"dc:title":["Aminoflavone Inhibits α6-integrin and Growth of Tamoxifen Resistant Breast Cancer"],"thesis:degree_discipline":["Basic Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T02:52:45Z"}