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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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ERα determines the chemo-resistant function of mutant p53 involving the switch between lincRNA-p21 and DDB2

Yu-Hao He1,2, Ming-Hsin Yeh3,4, Hsiao-Fan Chen2,5

  • 1The PhD Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 40402, Taiwan.

Molecular Therapy. Nucleic Acids
|September 30, 2021
PubMed

Insights

Mutant p53 promotes chemosensitivity by upregulating lincRNA-p21, but estrogen receptor alpha (ERα) confers chemoresistance by promoting DDB2. ER status dictates mutant p53

Area of Science:

  • Molecular Oncology
  • Cancer Biology
  • Genomics

Background:

  • Mutant p53 (mutp53) often impairs apoptosis and chemoresistance in breast cancer, but determinants are unclear.
  • Estrogen receptor alpha (ERα) role in mutp53-mediated chemoresistance needs further elucidation.

Purpose of the Study:

  • To investigate the role of mutp53 in chemotherapy response.
  • To identify mechanisms by which ERα influences mutp53 function in breast cancer.

Main Methods:

  • Analysis of mutp53 targeting of G-quadruplex and p53 response elements.
  • Quantification of lincRNA-p21 and DDB2 expression in relation to ER status.
  • Correlation of molecular findings with clinical response to neoadjuvant chemotherapy.

Main Results:

  • Mutp53 promotes chemosensitivity via G-quadruplex-mediated lincRNA-p21 induction.
  • ERα suppresses lincRNA-p21 and promotes DDB2, leading to chemoresistance.
  • lincRNA-p21 levels inversely correlate with ER status and DDB2; DDB2 is higher in ER-positive tumors.
  • ER status switches mutp53's target preference from lincRNA-p21 to DDB2.

Conclusions:

  • ERα status is a critical determinant of mutp53 oncogenic function in breast cancer chemoresistance.
  • Targeting lincRNA-p21 and DDB2 may enhance chemosensitivity in mutp53 breast cancers.
Keywords:
DDB2G-quadruplexchemotherapyestrogen receptorlincRNA-p21mutant p53

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