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Updated: Jul 7, 2026

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
11:12

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material

Published on: August 1, 2018

Jab1 is overexpressed in human breast cancer and is a downstream target for HER-2/neu

Ming-Chuan Hsu1, Chee-Yin Chai, Ming-Feng Hou

  • 1Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|February 5, 2008
PubMed

Insights

Jab1, a protein linked to cancer, is overexpressed in most breast tumors and its levels correlate with HER-2/neu. HER-2/neu signaling upregulates Jab1, which drives cancer cell growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Jab1 (c-Jun activation domain-binding protein 1) is a coactivator of AP-1 transcription factor and a subunit of the COP9 signalosome.
  • Jab1 is implicated as a potential oncogene involved in tumor suppressor p27(Kip1) degradation.
  • The regulation of Jab1 gene expression and its role in cancer remain largely uncharacterized.

Purpose of the Study:

  • To investigate the role of Jab1 gene expression in human breast tumors.
  • To determine the relationship between Jab1 expression and HER-2/neu signaling in breast cancer.
  • To elucidate the regulatory mechanism of Jab1 by HER-2/neu and its functional consequence.

Main Methods:

  • Analysis of Jab1 expression in 66 human breast tumor tissues.
  • Comparison of Jab1 expression in HER-2/neu-positive (MDA-MB-453) and HER-2/neu-negative (MCF-7) breast cancer cell lines.
  • Promoter activity assays to assess transcriptional regulation.
  • Pharmacological inhibition of HER-2/neu activity (Herceptin, AG825).
  • Ectopic expression of HER-2/neu.
  • Gene silencing of Jab1 using small interfering RNA (siRNA).

Main Results:

  • Jab1 was overexpressed in 80.3% of the analyzed breast tumors.
  • Jab1 expression significantly correlated with HER-2/neu overexpression (P=0.0318).
  • HER-2/neu-overexpressing cells showed higher Jab1 levels, which were reduced upon HER-2/neu inhibition.
  • Ectopic HER-2/neu expression increased Jab1 levels, indicating transcriptional activation.
  • Jab1 knockdown led to p27(Kip1) upregulation and G1 cell cycle arrest.

Conclusions:

  • Jab1 is a downstream target of HER-2/neu signaling in breast cancer.
  • Overexpression of Jab1 is closely linked to HER-2/neu expression in breast tumors.
  • Targeting Jab1 may represent a therapeutic strategy for HER-2/neu-positive breast cancers.

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