Related Experiment Video

Updated: Jun 22, 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 modulates malignant cell behavior, the expression of survivin and chemosensitivity in human breast cancer cells

Moltira Promkan1, Guangming Liu, Pimpicha Patmasiriwat

  • 1Department of Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine and SimmonsCooper Cancer Institute, Springfield, IL 62794-9677, USA.

International Journal of Cancer
|June 25, 2009
PubMed

Insights

BRCA1 protein loss in breast cancer cells increases proliferation and resistance to paclitaxel by upregulating survivin. Restoring BRCA1 function or reducing survivin re-sensitizes cells to chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • BRCA1 is a critical tumor suppressor protein, but its full functions in breast cancer remain incompletely understood.
  • Understanding BRCA1's role is vital for developing targeted breast cancer therapies.

Purpose of the Study:

  • To investigate the functional consequences of BRCA1 loss or mutation in human breast cancer cells.
  • To elucidate the molecular mechanisms linking BRCA1 to cell proliferation, survival, and chemosensitivity.

Main Methods:

  • Utilized short hairpin RNA (shRNA) to knockdown BRCA1 expression in wild-type breast cancer cell lines (MCF-7, MDA-MB-231).
  • Analyzed cell proliferation, anchorage-independent growth, migration, and invasion.
  • Assessed the expression of key proteins including p21/Waf1, p27Kip1, and survivin.
  • Investigated chemosensitivity to paclitaxel and the role of survivin using small interfering RNA (siRNA).
  • Compared findings with breast cancer cell lines harboring endogenous mutant or defective BRCA1 (MDA-MB-436, HCC1937).

Main Results:

  • BRCA1 knockdown significantly increased breast cancer cell proliferation, migration, invasion, and anchorage-independent growth.
  • Loss of BRCA1 led to decreased expression of p21/Waf1 and p27Kip1, and increased survivin expression.
  • BRCA1-deficient cells exhibited increased resistance to paclitaxel, which was directly linked to elevated survivin levels.
  • Restoring survivin knockdown via siRNA re-sensitized BRCA1-deficient cells to paclitaxel, confirming survivin's role in chemoresistance.

Conclusions:

  • BRCA1 acts as a tumor suppressor by inhibiting malignant behaviors, promoting cell cycle inhibitors (p21/Waf1, p27Kip1), and suppressing survivin.
  • Loss of BRCA1 function or expression results in increased survivin, leading to paclitaxel resistance in breast cancer.

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

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
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,...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...