title: Induced Expression of Cancer Stem Cell Markers ALDH1A3 and Sox-2 in Hierarchical Reconstitution of Apoptosis-resistant Human Breast Cancer Cells.
abstract: We established an experimental system that can induce p53-dependent apoptosis by doxycycline treatment to analyze characteristics of the apoptosis-resistant cancer cell subpopulation in the human breast cancer cell line HCC1937. Expression patterns of the stem cell markers, ALDH1A3 and Sox-2, the luminal differentiation marker, GATA3 and the proliferation index marker, Ki-67 were analyzed using immunostaining and fluorescence-activated cell sorting (FACS). After doxycycline treatment, the number of viable cells was gradually decreased over seven days in a time-dependent manner due to p53-induced apoptosis; however, the number of smaller-sized ALDH1A3+cells assessed by immunostaining increased sharply after 1 day of doxycycline treatment, suggesting their apoptosis-resistant nature. The expression of ALDH1A3 was also detected in 78% of small-sized Ki-67+proliferating progenitor cells, followed by the transient expression of GATA3, which presumably indicated the ability to differentiate into luminal progenitor cells. Although 42.2-58.5% of residual cells were positive for both ALDH1A3 and GATA3, their expression patterns exhibited an inverse correlation. The expression pattern of another stem cell marker, Sox-2, was similar, but more drastically altered after p53 induction compared with ALDH1A3. These findings may aid in understanding the hierarchical responses of cancer stem cells to therapeutic stresses.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.
authors.forename: Karin
authors.initials: K
authors.lastname: Kashii-Magaribuchi
authors.affiliation: Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.
authors.forename: Rie
authors.initials: R
authors.lastname: Takeuchi
authors.affiliation: Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Haisa
authors.affiliation: Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.
authors.forename: Akemi
authors.initials: A
authors.lastname: Sakamoto
authors.affiliation: Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.
authors.forename: Aimi
authors.initials: A
authors.lastname: Itoh
authors.affiliation: Graduate School of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Izawa
authors.affiliation: Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Isa
authors.affiliation: Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.
authors.forename: Mayu
authors.initials: M
authors.lastname: Fukuzawa
authors.affiliation: Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Graduate School of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts; Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts.
authors.forename: Rei
authors.initials: R
authors.lastname: Takahashi
keywords: ALDH1; GATA3; Sox-2; breast cancer; cancer stem cell