Related Experiment Video

Updated: Jun 18, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

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

Published on: August 12, 2015

BRCA1 185delAG mutant protein, BRAt, up-regulates maspin in ovarian epithelial cells

Joshua D O'Donnell1, Rebecca J Linger, Patricia A Kruk

  • 1Department of Pathology and Cell Biology, College of Medicine, University of South Florida,Tampa, FL 33612, USA.

Gynecologic Oncology
|November 13, 2009
PubMed
Abstract

Insights

BRCA1 mutation carriers with truncated BRAt protein show enhanced chemosensitivity. This involves increased maspin expression, a potential therapeutic target for ovarian cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Ovarian cancer presents significant challenges due to its aggressive nature and late detection.
  • Identifying early molecular changes in high-risk individuals, like BRCA1 mutation carriers, is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of the truncated BRCA1 protein (BRAt) in enhanced chemosensitivity.
  • To identify novel downstream targets of BRAt that promote apoptosis after chemotherapy.

Main Methods:

  • Utilized a cell culture model of normal human ovarian surface epithelial cells with and without the BRCA1 185delAG mutation.
  • Employed MTS, Western immunoblot, RT-PCR, luciferase reporter, and siRNA assays to identify BRAt targets.

Main Results:

  • Maspin was identified as a novel downstream target of BRAt, with BRAt increasing maspin expression and nuclear localization.
  • BRAt-mediated maspin expression is transcriptionally regulated via an AP1 site in the promoter region.
  • BRAt enhances chemosensitivity in ovarian cells through c-Jun, potentially involving maspin.

Conclusions:

  • BRAt-mediated chemosensitivity correlates with improved chemotherapeutic response in BRCA1 mutation carriers.
  • High nuclear maspin levels correlate with an improved prognostic outlook in ovarian tumors.
  • Understanding early molecular and pathological changes in high-risk ovarian cancer can reveal new therapeutic targets.

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

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors09:22

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity: