Related Experiment Video

Updated: Aug 7, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

The ERK1/2 pathway modulates nuclear PTEN-mediated cell cycle arrest by cyclin D1 transcriptional regulation

Ji-Hyun Chung1, Michael C Ostrowski, Todd Romigh

  • 1Human Cancer Genetics Program, Comprehensive Cancer Center, Department of Molecular and Cellular Biochemistry, Division of Human Genetics, The Ohio State University, Columbus, USA.

Human Molecular Genetics
|July 20, 2006
PubMed

Insights

Nuclear PTEN, a tumor suppressor, halts breast cancer cell growth by down-regulating cyclin D1 transcription. This process involves the mitogen-activated protein kinase (MAPK) pathway, highlighting nuclear PTEN

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • PTEN is a critical tumor suppressor gene frequently mutated in breast cancer.
  • PTEN's cell cycle arrest and apoptosis functions were primarily attributed to its cytoplasmic activities.
  • Nuclear localization of PTEN and its role in cell cycle regulation remained largely undefined.

Purpose of the Study:

  • To elucidate the mechanism by which nuclear PTEN suppresses cell growth.
  • To investigate the role of nuclear PTEN in regulating cyclin D1 transcription.
  • To determine the involvement of the MAPK pathway in nuclear PTEN-mediated growth suppression.

Main Methods:

  • Utilized MCF-7 Tet-Off breast cancer cell lines.
  • Employed stable expression of wild-type PTEN, nuclear localization-defective PTEN mutants, and empty vector controls.
  • Assessed PTEN localization, cyclin D1 transcription, and MAPK signaling.

Main Results:

  • Demonstrated that nuclear PTEN down-regulates cyclin D1 transcription.
  • Showed that nuclear PTEN specifically down-regulates MAPK.
  • Confirmed that nuclear localization is essential for PTEN's growth suppression activity via cyclin D1 and MAPK pathways.

Conclusions:

  • Nuclear PTEN plays a significant role in cell cycle suppression.
  • The down-regulation of cyclin D1 transcription by nuclear PTEN is mediated through MAPK signaling.
  • These findings provide evidence for nuclear PTEN's function in regulating carcinogenesis through cell cycle control.

More Related Videos

Analysis of Cell Cycle Position in Mammalian Cells12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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.
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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...