PMID- 33299647
OWN - NLM
STAT- MEDLINE
DCOM- 20211129
LR  - 20240330
IS  - 2095-3941 (Print)
IS  - 2095-3941 (Linking)
VI  - 17
IP  - 4
DP  - 2020 Nov 15
TI  - Role of chromosomal instability and clonal heterogeneity in the therapy response 
      of breast cancer cell lines.
PG  - 970-985
LID - 10.20892/j.issn.2095-3941.2020.0028 [doi]
AB  - OBJECTIVE: Chromosomal instability (CIN) is a hallmark of cancer characterized by 
      cell-to-cell variability in the number or structure of chromosomes, frequently 
      observed in cancer cell populations and is associated with poor prognosis, 
      metastasis, and therapeutic resistance. Breast cancer (BC) is characterized by 
      unstable karyotypes and recent reports have indicated that CIN may influence the 
      response of BC to chemotherapy regimens. However, paradoxical associations 
      between extreme CIN and improved outcome have been observed. METHODS: This study 
      aimed to 1) evaluate CIN levels and clonal heterogeneity (CH) in MCF7, ZR-751, 
      MDA-MB468, BT474, and KPL4 BC cells treated with low doses of tamoxifen (TAM), 
      docetaxel (DOC), doxorubicin (DOX), Herceptin (HT), and combined treatments 
      (TAM/DOC, TAM/DOX, TAM/HT, HT/DOC, and HT/DOX) by using fluorescence in situ 
      hybridization (FISH), and 2) examine the association with response to treatments 
      by comparing FISH results with cell proliferation. RESULTS: Intermediate CIN was 
      linked to drug sensitivity according to three characteristics: estrogen receptor 
      alpha (ERalpha) and HER2 status, pre-existing CIN level in cancer cells, and the CIN 
      induced by the treatments. ERalpha+/HER2- cells with intermediate CIN were sensitive 
      to treatment with taxanes (DOC) and anthracyclines (DOX), while ERalpha-/HER2-, 
      ERalpha+/HER2+, and ERalpha-/HER2+ cells with intermediate CIN were resistant to these 
      treatments. CONCLUSIONS: A greater understanding of CIN and CH in BC could assist 
      in the optimization of existing therapeutic regimens and/or in supporting new 
      strategies to improve cancer outcomes.
CI  - Copyright: (c) 2020, Cancer Biology & Medicine.
FAU - Vargas-Rondon, Natalia
AU  - Vargas-Rondon N
AD  - School of Biological Sciences, Universidad Pedagogica y Tecnologica de Colombia, 
      Tunja 150003, Colombia.
FAU - Perez-Mora, Erika
AU  - Perez-Mora E
AD  - School of Biological Sciences, Universidad Pedagogica y Tecnologica de Colombia, 
      Tunja 150003, Colombia.
FAU - Villegas, Victoria E
AU  - Villegas VE
AUID- ORCID: 0000-0003-4149-2307
AD  - Biology Program, Faculty of Natural Sciences, Universidad del Rosario, Bogota 
      111221, Colombia.
FAU - Rondon-Lagos, Milena
AU  - Rondon-Lagos M
AUID- ORCID: 0000-0002-3160-9316
AD  - School of Biological Sciences, Universidad Pedagogica y Tecnologica de Colombia, 
      Tunja 150003, Colombia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201215
PL  - China
TA  - Cancer Biol Med
JT  - Cancer biology & medicine
JID - 101588850
RN  - 0 (Anthracyclines)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Taxoids)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
MH  - Anthracyclines/administration & dosage
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Breast Neoplasms/drug therapy/*genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - *Chromosomal Instability
MH  - Estrogen Receptor alpha/metabolism
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Receptor, ErbB-2/metabolism
MH  - Receptors, Estrogen/*metabolism
MH  - Taxoids/administration & dosage
PMC - PMC7721098
OTO - NOTNLM
OT  - Breast cancer
OT  - FISH
OT  - chromosomal instability
OT  - clonal heterogeneity
OT  - therapy resistance
COIS- Conflicts of interest statement No potential conflicts of interest are disclosed.
EDAT- 2020/12/11 06:00
MHDA- 2021/11/30 06:00
PMCR- 2020/11/15
CRDT- 2020/12/10 05:58
PHST- 2020/01/18 00:00 [received]
PHST- 2020/05/20 00:00 [accepted]
PHST- 2020/12/10 05:58 [entrez]
PHST- 2020/12/11 06:00 [pubmed]
PHST- 2021/11/30 06:00 [medline]
PHST- 2020/11/15 00:00 [pmc-release]
AID - j.issn.2095-3941.2020.0028 [pii]
AID - 10.20892/j.issn.2095-3941.2020.0028 [doi]
PST - ppublish
SO  - Cancer Biol Med. 2020 Nov 15;17(4):970-985. doi: 
      10.20892/j.issn.2095-3941.2020.0028. Epub 2020 Dec 15.