Abstract
Purpose
Six-transmembrane epithelial antigen of prostate 1 (STEAP1) is a cell surface antigen
overexpressed in multiple cancers and is associated with malignancy and disease prognosis.
The aims of this study were to evaluate STEAP1 expression in breast cancer and to
determine the mechanisms involved.
Methods
STEAP1 expression was compared in normal breast tissue (n = 40), benign fibroadenoma
(n = 52), and primary breast cancer (n = 211) using immunohistochemistry. Quantitative
real-time polymerase chain reaction, Western blot analysis, and immunocytochemistry
were used to evaluate STEAP1 expression in 3 breast cancer cell lines and in a normal
mammary epithelial cell line. STEAP1 expression and its prognostic value in breast
cancer were verified using the Oncomine and Kaplan-Meier Plotter databases. Transfection
of cells to up-regulate or knock down STEAP1 expression was used to determine the
effect of STEAP1 on cell invasion and proliferation, and to evaluate its relationship
to epithelial–mesenchymal transition (EMT) progression.
Results
STEAP1 expression was lower in breast cancers cells, and low expression was associated
with a malignant phenotype and poor prognosis. Analysis of public databases supported
our conclusions. Knockdown of STEAP1 expression enhanced cellular invasion and migration
abilities, increased expression of EMT-related genes MMP2, MMP9, MMP13, VIM, and CDH2, and decreased CDH1 expression. Enhanced STEAP1 expression significantly inhibited cellular invasion
and migration abilities, decreased expression of the EMT-related genes, and increased
CDH1 expression. Up-regulation or knockdown of STEAP1 had little effect on cellular proliferation.
Conclusion
STEAP1 was down-regulated in breast cancer, inhibited metastasis of breast cancer,
and hampered the levels of EMT markers, which thus implicated STEAP1 in the suppression
of EMT.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic and PersonalCorporate R&D ProfessionalsOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Breast CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer.Breast Cancer Res. 2013; 15: R92
- Global cancer statistics, 2012.CA Cancer J Clin. 2015; 65: 87-108
- Risk factors for breast cancer among Filipino women in Manila.Int J Cancer. 2010; 126: 515-521
- Risk determination and prevention of breast cancer.Breast Cancer Res. 2014; 16: 446
- Correlating Ki67 and other prognostic markers with Oncotype DX recurrence score in early estrogen receptor-positive breast cancer.Asia Pac J Clin Oncol. 2018; 14: e161-e166
- Gene expression profiling in breast cancer: classification, prognostication, and prediction.Lancet. 2011; 378: 1812-1823
- A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.N Engl J Med. 2004; 351: 2817-2826
- STEAP: a prostate-specific cell-surface antigen highly expressed in human prostate tumors.Proc Natl Acad Sci U S A. 1999; 96: 14523-14528
- STEAP proteins: from structure to applications in cancer therapy.Mol Cancer Res. 2012; 10: 573-587
- STEAP1 is overexpressed in prostate cancer and prostatic intraepithelial neoplasia lesions, and it is positively associated with Gleason score.Urol Oncol. 2014; 32: 23-29
- High STEAP1 expression is associated with improved outcome of Ewing's sarcoma patients.Ann Oncol. 2012; 23: 2185-2190
- STEAP1 is associated with the invasive and oxidative stress phenotype of Ewing tumors.Mol Cancer Res. 2012; 10: 52-65
- The prognostic role of STEAP1 expression determined via immunohistochemistry staining in predicting prognosis of primary colorectal cancer: a survival analysis.Int J Mol Sci. 2016; 17: E592
- The Steap proteins are metalloreductases.Blood. 2006; 108: 1388-1394
- Production of large amounts of hydrogen peroxide by human tumor cells.Cancer Res. 1991; 51: 794-798
- Redox metabolism and malignancy.Curr Opin Pharmacol. 2010; 10: 362-368
- STEAP, a prostate tumor antigen, is a target of human CD8+ T cells.Cancer Immunol Immunother. 2006; 55: 1515-1523
- Recognition of six-transmembrane epithelial antigen of the prostate-expressing tumor cells by peptide antigen–induced cytotoxic T lymphocytes.Clin Cancer Res. 2005; 11: 4545-4552
- In vivo effects of vaccination with six-transmembrane epithelial antigen of the prostate: a candidate antigen for treating prostate cancer.Cancer Res. 2007; 67: 1344-1351
- Monoclonal antibodies to six-transmembrane epithelial antigen of the prostate-1 inhibit intercellular communication in vitro and growth of human tumor xenografts in vivo.Cancer Res. 2007; 67: 5798-5805
- Novel markers of subclinical disease for Ewing family tumors from gene expression profiling.Clin Cancer Res. 2007; 13: 6978-6983
- Identification of novel vascular targets in lung cancer.Br J Cancer. 2015; 112: 485-494
- STEAP1 is over-expressed in breast cancer and down-regulated by 17β-estradiol in MCF-7 cells and in the rat mammary gland.Endocrine. 2008; 34: 108-116
- Expression of STEAP1 and STEAP1B in prostate cell lines, and the putative regulation of STEAP1 by post-transcriptional and post-translational mechanisms.Genes Cancer. 2014; 5: 142-151
- The epithelial–mesenchymal transition: new insights in signaling, development, and disease.J Cell Biol. 2006; 172: 973
- The basics of epithelial mesenchymal transition.J Clin Invest. 2009; 119: 1420-1428
- Molecular requirements for epithelial–mesenchymal transition during tumor progression.Curr Opin Cell Biol. 2005; 17: 548-558
- Force measurements in E-cadherin–mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42.J Cell Biol. 2004; 167: 1183-1194
- Vimentin regulates scribble activity by protecting it from proteasomal degradation.Mol Biol Cell. 2009; 20: 2841-2855
- Cadherin switching.J Cell Sci. 2008; 121: 727-735
- Cadherins and the tumour progression: is it all in a switch?.Cancer Lett. 2002; 176: 123-128
- Cadherin switch in tumor progression.Ann N Y Acad Sci. 2004; 1014: 155
- Vimentin in cancer and its potential as a molecular target for cancer therapy.Cell Mol Life Sci. 2011; 68: 3033-3046
- Direct evidence linking expression of matrix metalloproteinase 9 (92 kDa gelatinase/collagenase) to the metastatic phenotype in transformed rat embryo cells.Proc Natl Acad Sci U S A. 1994; 91: 4293-4297
- Gelatinase B/MMP-9 in tumour pathogenesis and progression.Cancers (Basel). 2014; 6: 240-296
Article Info
Publication History
Published online: August 30, 2018
Accepted:
August 24,
2018
Received in revised form:
July 24,
2018
Received:
May 28,
2018
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.
