title: FOXA1 expression affects the proliferation activity of luminal breast cancer stem cell populations.
abstract: The expression of estrogen receptor is the key in most breast cancers (BC) and binding of estrogen receptor to the genome correlates to Forkhead protein (FOXA1) expression. We herein assessed the correlation between the cancer stem cell (CSC) population and FOXA1 expression in luminal BC. We established luminal BC cells derived from metastatic pleural effusion and analyzed the potency of CSC and related factors with established luminal BC cell lines. We also confirmed that mammosphere cultures have an increased aldehyde dehydrogenase-positive population, which is one of the CSC markers, compared with adherent culture cells. Using a quantitative PCR analysis, we found that mammosphere forming cells showed a higher expression of FOXA1 and stemness-related genes compared with adherent culture cells. Furthermore, the growth activity and colony-forming activity of 4-hydroxytamoxifen-treated BC cells were inhibited in a mammosphere assay. Interestingly, 4-hydroxytamoxifen-resistant cells had significantly increased FOXA1 gene expression levels. Finally, we established short hairpin RNA of FOXA1 (shFOXA1) MCF-7 cells and investigated the relationship between self-renewal potential and FOXA1 expression. As a result, we found no significant difference in the number of mammospheres but decreased colony formation in shFOXA1 MCF-7 cells compared with control. These results suggest that the expression of FOXA1 appears to be involved in the proliferation of immature BC cells rather than the induction of stemness-related genes and self-renewal potency of CSCs.
authors.affiliation: Department of Breast-Thyroid-Endocrine Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.|Laboratory of Regenerative Medicine and Stem Cell Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Tachi
authors.affiliation: Laboratory of Regenerative Medicine and Stem Cell Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shiraishi
authors.affiliation: Department of Breast-Thyroid-Endocrine Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Bando
authors.affiliation: Laboratory of Regenerative Medicine and Stem Cell Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Laboratory of Regenerative Medicine and Stem Cell Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Ikki
authors.initials: I
authors.lastname: Tsuboi
authors.affiliation: Laboratory of Regenerative Medicine and Stem Cell Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.|Ph.D. Program in Human Biology, School of Integrative and Grobal Majors, University of Tsukuba, Tsukuba, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Breast-Thyroid-Endocrine Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Hisato
authors.initials: H
authors.lastname: Hara
authors.affiliation: Laboratory of Regenerative Medicine and Stem Cell Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ohneda
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D014411:Neoplastic Stem Cells / Q000502:physiology*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018931:Antineoplastic Agents, Hormonal; C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D013629:Tamoxifen; C016601:afimoxifene
keywords: Breast cancer; FOXA1; cancer stem cells; mammosphere; tamoxifen resistance