Related Experiment Video

Updated: Mar 1, 2026

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors
09:22

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

6.0K

Effect of TPA and HTLV-1 Tax on BRCA1 and ERE controlled genes expression

Azhar Jabareen1, Aya Abu-Jaafar1, Ammar Abou-Kandil1

  • 1a Shraga Segal Department of Microbiology and Immunology , Faculty of Health Sciences, Ben Gurion University of the Negev , Beer Sheva , Israel.

Cell Cycle (Georgetown, Tex.)
|June 9, 2017
PubMed

Insights

Tumor suppressor BRCA1, crucial for breast and ovarian cancer prevention, is activated by estrogen receptor alpha (ERα). TPA treatment significantly boosted BRCA1 and ERE-regulated gene expression, independent of ERα signaling.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • BRCA1 is a key tumor suppressor involved in breast and ovarian cancer risk.
  • Estrogen receptor alpha (ERα) typically activates BRCA1 expression via classical and non-classical pathways.
  • Previous studies showed HTLV-1 Tax inhibits ERα-induced BRCA1 but stimulates ERE-dependent genes.

Purpose of the Study:

  • To investigate the effect of TPA, a PKC activator, on BRCA1 and ERE-regulated gene expression in MCF-7 cells.
  • To determine the role of Tax and ERα signaling in TPA-mediated gene expression.
  • To explore the involvement of PKC, NFκB, and 53BP1 in TPA's effects.

Main Methods:

  • MCF-7 cell culture and treatment with TPA and E2.
  • Quantitative PCR to assess gene expression (BRCA1, ERE-regulated genes).
  • Chromatin immunoprecipitation (ChIP) assay to evaluate ERα binding.
  • Overexpression studies with 53BP1.

Main Results:

  • TPA strongly stimulated BRCA1 and ERE expression independently of E2.
  • Tax did not significantly alter TPA's effects on BRCA1 and ERE expression.
  • TPA's activity appears dependent on PKC but not NFκB, with 53BP1 potentially involved.
  • ChIP assays indicated TPA does not interfere with ERα binding to the BRCA1 promoter or ERE regions.

Conclusions:

  • TPA activates BRCA1 and ERE-regulated gene expression in MCF-7 cells, likely via PKC-dependent but ERα-independent pathways.
  • The tumor suppressor protein 53BP1 may play a role in modulating TPA's stimulatory effects.
  • These findings suggest novel signaling mechanisms influencing BRCA1 expression beyond the classical ERα pathway.
Keywords:
BRCA-1EREERαHTLV-1TPATax

More Related Videos

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA108:53

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

Published on: February 17, 2011

15.1K
Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

9.6K

Related Concept Videos

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
56
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.9K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.8K
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
13.6K