Related Experiment Video

Updated: Jun 14, 2026

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
09:40

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation

Published on: June 27, 2017

IGFBP-2 expression in MCF-7 cells is regulated by the PI3K/AKT/mTOR pathway through Sp1-induced increase in

Matei Mireuta1, Andrew Darnel, Michael Pollak

  • 1Departments of Medicine and Oncology, Lady Davis Institute for Medical Research, Montreal SMBD Jewish General Hospital, and McGill University, Montreal, Quebec, CanadaH3T 1E2.

Growth Factors (Chur, Switzerland)
|April 8, 2010
PubMed

Insights

The PI3K/AKT/mTOR pathway controls insulin-like growth factor binding protein 2 (IGFBP-2) levels in breast cancer cells by regulating its mRNA abundance. This involves the Sp1 transcription factor binding to a key DNA region, impacting IGFBP-2 expression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Insulin-like growth factor binding protein 2 (IGFBP-2) is linked to cancer development.
  • The PI3K/AKT/mTOR pathway influences IGFBP-2 protein levels in MCF-7 breast cancer cells.
  • The precise molecular mechanisms of this regulation remain unclear.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which the PI3K/AKT/mTOR pathway regulates IGFBP-2 in MCF-7 cells.
  • To investigate the role of mRNA abundance and transcription in this regulation.

Main Methods:

  • Investigated the effect of PI3K/AKT/mTOR pathway modulators on IGFBP-2 mRNA and protein levels.
  • Assessed the role of the Sp1 transcription factor and its binding site in regulating IGFBP-2 transcription.
  • Utilized IGF-1, Rapamycin, and LY294002 treatments in MCF-7 cells.

Main Results:

  • The PI3K/AKT/mTOR pathway regulates IGFBP-2 protein levels via modulation of IGFBP-2 mRNA abundance.
  • Regulation occurs at the transcriptional level, mediated by Sp1 binding to a critical promoter region.
  • IGF-1 increased Sp1 nuclear abundance, IGFBP-2 mRNA, and protein levels.
  • Rapamycin and LY294002 decreased Sp1 nuclear abundance, IGFBP-2 mRNA, and protein levels.

Conclusions:

  • The PI3K/AKT/mTOR pathway controls IGFBP-2 expression in MCF-7 cells by regulating Sp1-driven transcription.
  • This study provides a mechanistic link between the PI3K/AKT/mTOR pathway and IGFBP-2 levels in breast cancer cells.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells07:22

Isolation and Differentiation of Stromal Vascular Cells to Beige/Brite Cells

Published on: March 28, 2013

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...