SCUBE2 suppresses breast tumor cell proliferation and confers a favorable prognosis in invasive breast cancer

Chien Jui Cheng, Yuh Charn Lin, Ming Tzu Tsai, Ching Shyang Chen, Mao-Chih Hsieh, Chi Long Chen, Ruey Bing Yang

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Signal peptide-CUB-epidermal growth factor-like domain-containing protein 2 (SCUBE2), originally identified from the endothelium and several nonendothelial primary ceD types, was recently shown to be expressed in invasive breast carcinomas. However, the protein localization and biological significance of SCUBE2 in breast cancer are unknown. In this report, we show by anti-SCUBE2 immunostaining that SCUBE2 is mainly expressed in vascular endothelial and mammary ductal epithelial cells in normal breast tissue. In addition, we observed positive staining for SCUBE2 in 55% (86 of 156) of primary breast tumors. Patients with positive SCUBE2 protein-expressing tumors had better prognosis than those with negative SCUBE2 protein-expressing tumors in terms of disease-free survival. Multivariate analysis confirmed SCUBE2 protein expression as an independent prognostic factor for disease-free survival. Furthermore, overexpression of ectopic SCUBE2 protein resulted in suppression of MCF-7 breast cancer cell proliferation and reduced MCF-7 xenograft tumor growth in nude mice. Molecular and biochemical analyses revealed that the COOH terminal region of SCUBE2 directly bound to and antagonized bone morphogenetic protein activity. Together, our results show for the first time that altered SCUBE2 expression is important in breast cancer progression and SCUBE2 may serve as a useful prognostic marker.

Original languageEnglish
Pages (from-to)3634-3641
Number of pages8
JournalCancer Research
Volume69
Issue number8
DOIs
Publication statusPublished - Apr 15 2009

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Cell Proliferation
Breast Neoplasms
Proteins
Disease-Free Survival
Breast
Neoplasms
Bone Morphogenetic Proteins
Protein Sorting Signals
Epidermal Growth Factor
Heterografts
Nude Mice
Endothelium
Blood Vessels
Multivariate Analysis
Epithelial Cells
Staining and Labeling
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

SCUBE2 suppresses breast tumor cell proliferation and confers a favorable prognosis in invasive breast cancer. / Cheng, Chien Jui; Lin, Yuh Charn; Tsai, Ming Tzu; Chen, Ching Shyang; Hsieh, Mao-Chih; Chen, Chi Long; Yang, Ruey Bing.

In: Cancer Research, Vol. 69, No. 8, 15.04.2009, p. 3634-3641.

Research output: Contribution to journalArticle

Cheng, Chien Jui ; Lin, Yuh Charn ; Tsai, Ming Tzu ; Chen, Ching Shyang ; Hsieh, Mao-Chih ; Chen, Chi Long ; Yang, Ruey Bing. / SCUBE2 suppresses breast tumor cell proliferation and confers a favorable prognosis in invasive breast cancer. In: Cancer Research. 2009 ; Vol. 69, No. 8. pp. 3634-3641.
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