Estrogen and insulin-like growth factor-I (IGF-I) independently down-regulate critical repressors of breast cancer

Related Experiment Video

Updated: Jun 2, 2026

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration
11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

Angelo J Casa1, Adam S Potter, Simeen Malik

  • 1Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.

Breast Cancer Research and Treatment
|May 5, 2011
PubMed

Insights

Estrogen receptor alpha (ERα) and insulin-like growth factor (IGF) signaling co-regulate genes impacting breast cancer prognosis. This cross-talk, particularly gene repression, suggests combined pathway targeting for clinical benefit.

Area of Science:

  • Molecular biology
  • Cancer research
  • Endocrinology

Background:

  • Estrogen receptor alpha (ERα) and insulin-like growth factor (IGF) signaling are crucial in mammary development and breast cancer.
  • The intricate cross-talk between ERα and IGF signaling, especially at the transcriptional level, is not fully elucidated.

Purpose of the Study:

  • To investigate the transcriptional cross-talk between ERα and IGF signaling pathways in breast cancer cells.
  • To identify genes co-regulated by estradiol (E2) and IGF-I and assess their impact on breast cancer prognosis.

Main Methods:

  • Microarray analysis of MCF-7 breast cancer cells treated with E2 or IGF-I.
  • Gene expression profiling at 3 and 24 hours post-treatment.
  • Bioinformatic analysis to identify co-regulated genes and correlate expression with patient outcomes.

Main Results:

  • IGF-I modulated significantly more genes than E2; many genes were co-regulated by both ligands.
  • Co-regulated genes showed a correlation with poor human breast cancer prognosis, with an enrichment of repressed transcripts.
  • Down-regulation of potential tumor suppressors like B-cell linker (BLNK) by both IGF-I and E2 was observed.

Conclusions:

  • ERα and IGF-I co-regulate a specific set of genes influencing breast cancer outcomes.
  • Gene repression is a key feature of this cross-talk, occurring independently at the receptor level but converging downstream via common kinases (PI3K, MEK).
  • Co-targeting of ERα and IGF-IR signaling may be a clinically relevant strategy for tumors with active signaling in both pathways.

More Related Videos

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

Related Concept Videos

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...
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...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
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...