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Activating transcription factor 3 mediates apoptosis and cell cycle arrest in TP53-mutated anaplastic thyroid cancer

Abolfazl Kooti1, Haniyeh Abuei1, Alireza Jaafari2

  • 1Division of Medical Biotechnology, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

Thyroid Research
|July 31, 2024
PubMed
Abstract

Insights

Overexpressing Activating Transcription Factor 3 (ATF3) suppressed mutant p53 activity in anaplastic thyroid carcinoma (ATC) cells. This suggests ATF3 as a potential therapeutic target for p53-mutated thyroid cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Loss of p53 function is critical in thyroid cancer progression, especially in anaplastic thyroid carcinoma (ATC).
  • ATC's poor prognosis necessitates novel therapeutic targets due to chemoresistance.
  • Activating Transcription Factor 3 (ATF3) inhibits mutant p53 oncogenic activity and acts as a tumor suppressor in TP53-mutated cancers.

Purpose of the Study:

  • To investigate the effect of ectopic ATF3 overexpression on chemo-resistant 8305C thyroid cancer cells with a mutant p53 (R273C).
  • To assess ATF3's potential as a therapeutic target in p53-mutated thyroid cancers.

Main Methods:

  • Transfection of 8305C cells with pCMV6-ATF3 plasmid.
  • Assessment of cell viability, apoptosis, and cell cycle using MTT assay, fluorescent microscopy, and flow cytometry.
  • Western blotting to evaluate p53 protein levels and RT-qPCR for TP53, TAp63, ΔNp63, and SHARP1 mRNA expression.

Main Results:

  • ATF3 overexpression significantly reduced cell viability and induced apoptosis and cell cycle arrest in 8305C cells.
  • ATF3 overexpression increased mutant p53 protein levels in 8305C cells.
  • Elevated TAp63 and SHARP1 mRNA levels and decreased ΔNp63 mRNA levels were observed in ATF3-expressing cells.

Conclusions:

  • Ectopic ATF3 expression suppresses oncogenic mutant p53 activity in chemo-resistant thyroid cancer cells.
  • Therapeutic strategies targeting ATF3 expression or its interaction with mutant p53 show promise for treating p53-mutated metastatic thyroid cancer.
Keywords:
8305CATF3Mutant p53SHARP1TAp63Thyroid cancerΔNp63

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