Evidence map›Paper›PMID 33294429›Full record

ArticleStem cell investigation2020

Tamoxifen induces stem-like phenotypes and multidrug resistance by altering epigenetic regulators in ERα+ breast cancer cells.

Aparna Kalyanaraman, Dhanavathy Gnanasampanthapandian, Prasad Shanmughan, Puneet Kishore, Satish Ramalingam, Rathnaswami Arunachalam, Selvaraj Jayaraman, Ilango Kaliappan, Ganesh Munuswamy-Ramanujam, Ilangovan Ramachandran and 4 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 42% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Selective Estrogen Receptor Modulators' (SERMs) Influence onInternational journal of molecular sciences · 2024
    Article
  5. ERα promotesGland surgery · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Aparna KalyanaramanCancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Kancheepuram, India.
Dhanavathy GnanasampanthapandianCancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Kancheepuram, India.
Prasad ShanmughanCancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Kancheepuram, India.
Puneet KishoreCancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Kancheepuram, India.
Satish RamalingamDepartment of Genetic Engineering, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Kancheepuram, India.
Rathnaswami ArunachalamDepartment of Surgical Gastroenterology, SRM Medical College Hospital and Research Center, Kattankulathur, Kancheepuram, India.
Selvaraj JayaramanDepartment of Biochemistry, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Velappanchavadi, Velappanchavadi, Chennai, India.
Ilango KaliappanDepartmemt of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, India.
Ganesh Munuswamy-RamanujamInterdisciplinary Institute of Indian System of Medicine, SRM Institute of Science and Technology, Kattankulathur, India.
Ilangovan RamachandranDepartment of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani campus, Chennai, India.
Yuvaraj SambandamDepartment of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani campus, Chennai, India.
Muralidharan AnbalaganDepartment of Structural and Cellular Biology, Tulane University, New Orleans, LA, USA.
Parthasarathy ChandrakesanDepartment of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Kanagaraj PalaniyandiCancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Kancheepuram, India.
SRM Institute of Science and Technology · INUniversity of Madras · INSaveetha University · INTulane University · USUniversity of Oklahoma Health Sciences Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTo understand the mechanism underlying tamoxifen-induced multidrug resistance (MDR) and stem-like phenotypes in breast cancer cells, we treated the MCF-7 cells with 4-hydroxy-tamoxifen (TAM) for 6 months continuously and established MCF-7 tamoxifen resistance (TR) phenotypes.

methodsIn the present study, the following methods were used: cell viability assay, colony formation, cell cycle analysis, ALDEFLUOR assay, mammosphere formation assay, chromatin immunoprecipitation (ChIP) assay, PCR array, western blot analysis and quantitative reverse transcription polymerase chain reaction (QRT-PCR).

resultsThe expression of ERα was significantly higher in MCF7-TR cells when compared with parental MCF-7 cells. MCF7-TR cells exposed to TAM showed a significant increase in the proliferation and rate of colony formation. The number of cancer stem cells was higher in MCF7-TR cells as observed by the increase in the number of ALDH+ cells. Furthermore, the number of mammospheres formed from the FACS-sorted ALDH+ cells was higher in MCF7-TR cells. Using PCR array analysis, we were able to identify that the long-term exposure of TAM leads to alterations in the epigenetic and MDR stem cell marker genes. Furthermore, western blot analysis demonstrated elevated levels of Notch-1 expression in MCF-TR cells compared with MCF-7 cells. Chromatin immunoprecipitation (ChIP) assay revealed that Notch-1 enhanced the cyclin D1 expression significantly in these cells. In addition, we observed that MCF7-TR cells were resistant to doxorubicin but not the MCF-7 cells.

conclusionsIn the present study, we conclude that the treatment with tamoxifen induces multiple epigenetic alterations that lead to the development of MDR and stem-like phenotypes in breast cancers. Therefore, our study provides better insights to develop novel treatment regime to control the progression of breast cancer.

Indexed as

breast cancer stem cellsepigeneticsmultidrug resistance (MDR)Notch-1Tamoxifen resistance (TR)

Identifiers

PMID33294429
PMCPMC7715663
OpenAlexW3095897655

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.