Tissue factor is involved in retinoblastoma cell proliferation via both the Akt and extracellular signal-regulated

Byung Joo Lee1, Jeong Hun Kim, Seung Hoon Woo

  • 1Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, and Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea.

Oncology Reports
|May 28, 2011
PubMed

Insights

Tissue factor (TF) drives retinoblastoma cell proliferation. Blocking the TF pathway with TF pathway inhibitor (TFPI) suppressed tumor growth and key signaling pathways, offering a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Ophthalmology

Background:

  • Tissue factor (TF) is implicated in tumor progression.
  • The role and expression of TF in retinoblastoma remain uncharacterized.

Purpose of the Study:

  • To investigate the expression and function of TF in retinoblastoma.
  • To determine if TF pathway blockade can inhibit retinoblastoma cell proliferation.

Main Methods:

  • TF expression analysis in an orthotopic retinoblastoma mouse model.
  • Assessment of TF pathway inhibitor (TFPI) effects on FGF2-stimulated retinoblastoma cells.
  • Evaluation of Akt and ERK1/2 phosphorylation levels.

Main Results:

  • TF is selectively expressed in highly proliferative areas of retinoblastoma tumors.
  • FGF2 treatment increased TF expression and retinoblastoma cell proliferation.
  • TFPI significantly inhibited FGF2-induced proliferation and phosphorylation of Akt and ERK1/2.

Conclusions:

  • TF expression is closely linked to retinoblastoma cell proliferation.
  • TFPI demonstrates potential as a therapeutic agent by inhibiting retinoblastoma growth via Akt and ERK1/2 pathways.

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,...
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,...
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...
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...
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...