title: Effect of low doses of estradiol and tamoxifen on breast cancer cell karyotypes.
abstract: Evidence supports a role of 17&-estradiol (E2) in carcinogenesis and the large majority of breast carcinomas are dependent on estrogen. The anti-estrogen tamoxifen (TAM) is widely used for both treatment and prevention of breast cancer; however, it is also carcinogenic in human uterus and rat liver, highlighting the profound complexity of its actions. The nature of E2- or TAM-induced chromosomal damage has been explored using relatively high concentrations of these agents, and only some numerical aberrations and chromosomal breaks have been analyzed. This study aimed to determine the effects of low doses of E2 and TAM (10(&8 )mol L(&1) and 10(&6 )mol L(&1) respectively) on karyotypes of MCF7, T47D, BT474, and SKBR3 breast cancer cells by comparing the results of conventional karyotyping and multi-FISH painting with cell proliferation. Estrogen receptor (ER)-positive (+) cells showed an increase in cell proliferation after E2 treatment (MCF7, T47D, and BT474) and a decrease after TAM treatment (MCF7 and T47D), whereas in ER& cells (SKBR3), no alterations in cell proliferation were observed, except for a small increase at 96 h. Karyotypes of both ER+ and ER& breast cancer cells increased in complexity after treatments with E2 and TAM leading to specific chromosomal abnormalities, some of which were consistent throughout the treatment duration. This genotoxic effect was higher in HER2+ cells. The ER&/HER2+ SKBR3 cells were found to be sensitive to TAM, exhibiting an increase in chromosomal aberrations. These in vitro results provide insights into the potential role of low doses of E2 and TAM in inducing chromosomal rearrangements in breast cancer cells.
authors.affiliation: Department of Medical SciencesUniversity of Turin, Turin, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Rondón-Lagos
authors.affiliation: Department of Medical SciencesUniversity of Turin, Turin, Italy Natural and Mathematical Sciences FacultyUniversidad del Rosario, Bogotá, Colombia.
authors.forename: Nelson
authors.initials: N
authors.lastname: Rangel
authors.affiliation: Pathology DivisionAzienda Ospedaliera Città della Salute e della Scienza di Torino, Turin, Italy.
authors.forename: Ludovica Verdun
authors.initials: LV
authors.lastname: Di Cantogno
authors.affiliation: Department of Medical SciencesUniversity of Turin, Turin, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Annaratone
authors.affiliation: Department of Medical SciencesUniversity of Turin, Turin, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Castellano
authors.affiliation: Department of Medical SciencesUniversity of Turin, Turin, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Russo
authors.affiliation: Department of Public Health and PediatricsUniversity of Turin, Turin, Italy.
authors.forename: Tilde
authors.initials: T
authors.lastname: Manetta
authors.affiliation: Department of Medical SciencesUniversity of Turin, Turin, Italy caterina.marchio@unito.it anna.sapino@ircc.it.
authors.forename: Caterina
authors.initials: C
authors.lastname: Marchiò
authors.affiliation: Department of Medical SciencesUniversity of Turin, Turin, Italy Candiolo Cancer InstituteFPO-IRCCS, Candiolo, Italy caterina.marchio@unito.it anna.sapino@ircc.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000633:toxicity*; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004958:Estradiol / Q000633:toxicity*; D004965:Estrogen Antagonists / Q000633:toxicity*; D006801:Humans; D059785:Karyotype; D013629:Tamoxifen / Q000633:toxicity*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D013629:Tamoxifen; D004958:Estradiol
keywords: breast cancer cells; chromosomal abnormalities; chromosomal instability; estradiol; tamoxifen