Inactivated tumor suppressor Rb by nitric oxide promotes mitosis in human breast cancer cells

Related Experiment Video

Updated: Aug 24, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

Ziv Radisavljevic1

  • 1Department of Cancer Cell Biology, Harvard University, School of Public Health, Boston, Massachusetts 02115, USA. zradisav@hsph.harvard.edu

Journal of Cellular Biochemistry
|April 20, 2004
PubMed

Insights

Nitric oxide (NO) inactivates the retinoblastoma (Rb) tumor suppressor protein in breast cancer cells. This promotes cell proliferation by increasing the G2/M phase via a p53-independent pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cell cycle progression is regulated by key proteins like the retinoblastoma (Rb) tumor suppressor.
  • Nitric oxide (NO) is implicated in various cellular processes, including cancer, but its role in Rb regulation is unclear.
  • Human breast cancer cell line T47D produces significant amounts of NO.

Purpose of the Study:

  • To investigate the effect of nitric oxide (NO) on the retinoblastoma (Rb) tumor suppressor protein in T47D breast cancer cells.
  • To determine if NO-induced Rb inactivation influences cell cycle progression and proliferation.
  • To explore the involvement of the p53 pathway in NO-mediated effects on breast cancer cells.

Main Methods:

  • Treatment of T47D breast cancer cells with nitric oxide (NO).
  • Analysis of retinoblastoma (Rb) protein phosphorylation status.
  • Assessment of cell cycle phase distribution (G1/S, G2/M).
  • Evaluation of p53 phosphorylation at serine-15.

Main Results:

  • Nitric oxide (NO) treatment led to increased phosphorylation and inactivation of the Rb tumor suppressor protein.
  • NO exposure resulted in a shift towards the G2/M phase, indicating increased cell proliferation.
  • No significant changes were observed in p53 phosphorylation at serine-15, suggesting a p53-independent mechanism.

Conclusions:

  • Nitric oxide (NO) promotes breast cancer cell proliferation by phosphorylating and inactivating the Rb tumor suppressor protein.
  • The NO-induced cell proliferation occurs through a p53-independent pathway, primarily involving the Rb pathway.
  • Targeting the NO-Rb interaction may offer a novel therapeutic strategy for breast cancer treatment.

More Related Videos

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module10:39

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module

Published on: June 18, 2015

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,...
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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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.