CTCFL expression is associated with cerebral vascular abnormalities

Leyla Sati1, Bikem Soygur2, Ethem Goksu3

  • 1Department of Histology and Embryology, Akdeniz University School of Medicine, Antalya, Turkey.

Tissue & Cell
|March 23, 2021
PubMed

Insights

Cancer-testis gene CTCFL (Cell- and testis-associated protein) overexpression in mice caused vascular brain malformations. CTCFL was also found in human cerebral cavernous malformations (CCM) and arteriovenous malformations (AVM), suggesting a role in human vascular development.

Area of Science:

  • Developmental Biology
  • Genetics
  • Oncology

Background:

  • The cancer-testis gene CTCFL (Cell- and testis-associated protein) is aberrantly expressed in malignant cells.
  • Previous studies demonstrated that inappropriate Ctcfl expression in mice leads to fetal developmental issues and postnatal lethality.
  • Affected mouse pups exhibited severe vascular abnormalities, including brain hemorrhages resembling human cerebral cavernous malformations (CCM) and arteriovenous malformations (AVM).

Purpose of the Study:

  • To investigate the presence of CCM-related proteins (CCM1/KRIT1, CCM2/malcavernin, CCM3/PDCD10) in Ctcfl transgenic mice.
  • To determine if CTCFL is expressed in human CCM and AVM tissues.
  • To explore the role of CTCFL in vascular development.

Main Methods:

  • Utilized a tetracycline-inducible Ctcfl transgene in mice to study gene expression effects.
  • Analyzed vascular markers (CD31, vWF, α-SMA) in transgenic animals.
  • Examined the expression of CCM-related proteins in mouse models.
  • Detected CTCFL expression in human CCM and AVM tissue samples.

Main Results:

  • Ctcfl transgenic animals showed increased CD31 expression in specific vascular areas.
  • CCM-related proteins CCM1/KRIT1, CCM2/malcavernin, and CCM3/PDCD10 were aberrantly expressed in the heads of transgenic mice.
  • CTCFL expression was confirmed in human CCM and AVM tissues.

Conclusions:

  • Induced CTCFL expression in mice results in vascular brain malformations.
  • The presence of CTCFL in human vascular malformations suggests a role in human vascular development.
  • These findings offer new insights into CTCFL's function in vascular development.