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Splicing factor Tra2-beta1 is specifically induced in breast cancer and regulates alternative splicing of the CD44

Dirk O Watermann1, Yesheng Tang, Axel Zur Hausen

  • 1Department of Obstetrics and Gynecology, University of Freiburg, Freiburg, Germany.

Cancer Research
|May 3, 2006
PubMed

Insights

The splicing factor Tra2-beta1 enhances CD44 exon inclusion, particularly in breast cancer. Its increased expression in tumors suggests a role in cancer progression and metastasis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • RNA Splicing

Background:

  • The CD44 gene exhibits extensive alternative splicing, involving variable exons crucial for various cellular functions.
  • Aberrant splicing of CD44 is linked to tumor progression and metastasis in several human cancers, including breast cancer.
  • Exon v4 of CD44 contains enhancer sequences essential for its inclusion and binding of specific nucleic acid-binding proteins.

Purpose of the Study:

  • To investigate the role of the serine/arginine-rich (SR) splicing factor human Tra2-beta1 (hTra2-beta1) in the alternative splicing of CD44.
  • To determine if hTra2-beta1 influences the inclusion of CD44 exons v4 and v5.
  • To assess the expression levels of hTra2-beta1 in human breast cancer tissues compared to non-pathologic controls.

Main Methods:

  • In vivo splicing assays were performed to evaluate the effect of hTra2-beta1 on CD44 exon v4 and v5 inclusion.
  • The synergistic effects of hTra2-beta1 with YB-1 protein were examined.
  • Matched pair analysis of human breast cancer and nonpathologic tissue samples was conducted to quantify Tra2-beta1 RNA and protein levels.

Main Results:

  • hTra2-beta1 significantly enhanced the in vivo inclusion of CD44 exons v4 and v5, acting synergistically with YB-1.
  • The enhancer sequence within exon v4 was required for hTra2-beta1-mediated activation.
  • A significant induction of Tra2-beta1 was observed in invasive breast cancer tissues at both RNA and protein levels compared to controls.

Conclusions:

  • hTra2-beta1 plays a key role in promoting the inclusion of CD44 exons v4 and v5, potentially through interaction with enhancer elements.
  • The elevated expression of Tra2-beta1 in breast cancer suggests its involvement in the generation of CD44 isoforms associated with tumor progression.
  • These findings highlight Tra2-beta1 as a potential factor contributing to breast cancer metastasis.

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