Related Experiment Video

Updated: Jul 10, 2026

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene
08:18

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene

Published on: December 31, 2014

Cell growth inhibition by okadaic acid involves gut-enriched Kruppel-like factor mediated enhanced expression of

Liyue Zhang1, Anil Wali, Chilakamarti V Ramana

  • 1John D. Dingell V.A. Medical Center and Department of Internal Medicine, Wayne State University, Detroit, Michigan 48201, USA.

Cancer Research
|November 3, 2007
PubMed

Insights

Okadaic acid (OA) suppresses human breast cancer (HBC) growth by increasing c-Myc expression, a key factor in cell growth. This mechanism involves the transcription factor GKLF, highlighting a novel therapeutic target for breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Okadaic acid (OA) is known to suppress human breast cancer (HBC) cell growth.
  • Previous studies indicated OA's effects involve elevated oncogene expression (c-myc, c-fos) and apoptosis.
  • c-Myc is a critical regulator of diverse cell growth pathways.

Purpose of the Study:

  • To investigate if c-Myc induction by OA or cycloheximide contributes to HBC growth inhibition.
  • To elucidate the underlying mechanisms of OA-induced c-Myc expression and its role in HBC growth suppression.

Main Methods:

  • Human breast cancer cell lines were treated with OA, cycloheximide, or Taxol.
  • c-Myc expression levels were analyzed following treatments.
  • c-Myc depletion experiments were conducted.
  • Analysis of the c-myc promoter region, including gel mobility shift assays and mutation studies.
  • Identification and functional analysis of transcription factors binding to the c-myc promoter.

Main Results:

  • OA and cycloheximide treatments suppressed HBC cell growth and induced c-Myc expression.
  • Depletion of c-Myc enhanced HBC cell viability when treated with OA or cycloheximide, but not Taxol.
  • OA induced c-myc transcription via a specific promoter region (-11 to +70).
  • Nuclear proteins, including GKLF, bind to this OA-responsive promoter region.
  • OA treatment increased GKLF expression, and GKLF consensus sequence mutations abrogated OA responsiveness.

Conclusions:

  • OA-dependent attenuation of HBC growth is partly mediated by GKLF-enhanced c-myc transcription.
  • GKLF acts as a zinc finger transcription factor regulating c-myc in response to OA.
  • This study reveals a novel mechanism involving GKLF and c-Myc in breast cancer growth suppression by OA.

More Related Videos

Yeast As a Chassis for Developing Functional Assays to Study Human P5314:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

Related Concept Videos

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...
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...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
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...
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...