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. 2011:2011:723650.
doi: 10.1155/2011/723650. Epub 2011 Oct 3.

Novel stromal biomarkers in human breast cancer tissues provide evidence for the more malignant phenotype of estrogen receptor-negative tumors

Zahraa I Khamis  1 , Ziad J Sahab, Stephen W Byers, Qing-Xiang Amy Sang
Affiliations

Novel stromal biomarkers in human breast cancer tissues provide evidence for the more malignant phenotype of estrogen receptor-negative tumors

Zahraa I Khamis et al. J Biomed Biotechnol. 2011.

Abstract

Research efforts were focused on genetic alterations in epithelial cancer cells. Epithelial-stromal interactions play a crucial role in cancer initiation, progression, invasion, angiogenesis, and metastasis; however, the active role of stroma in human breast tumorigenesis in relation to estrogen receptor (ER) status of epithelial cells has not been explored. Using proteomics and biochemical approaches, we identified two stromal proteins in ER-positive and ER-negative human breast cancer tissues that may affect malignant transformation in breast cancer. Two putative biomarkers, T-cell receptor alpha (TCR-α) and zinc finger and BRCA1-interacting protein with a KRAB domain (ZBRK1), were detected in leukocytes of ER-positive and endothelial cells of ER-negative tissues, respectively. Our data suggest an immunosuppressive role of leukocytes in invasive breast tumors, propose a multifunctional nature of ZBRK1 in estrogen receptor regulation and angiogenesis, and demonstrate the aggressiveness of ER-negative human breast carcinomas. This research project may identify new stromal drug targets for the treatment of breast cancer patients.

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Figures

Figure 1
Figure 1
2DE: two-dimensional gel electrophoresis (2DE) of epithelial cells (Epi), myofibroblasts (Myo), leukocytes (leuk), and endothelial cells (Endo) proteins separated from estrogen receptor-positive and estrogen receptor-negative breast cancer cells using antibody-bound magnetic beads. First dimension was performed on a pH 4 to 7 isoelectric focusing gels and the second dimension was done utilizing 10% polyacrylamide gels. Gels were stained by Sypro Ruby. Arrows point to identified proteins spots.
Figure 2
Figure 2
T cell receptor alpha spectra: T-cell receptor alpha was detected in the leukocytes of estrogen receptor-positive breast cancer not in that of estrogen receptor negative. LC-Q-TOF MS/MS spectra of GITLSVRP peptide generated from the trypsin digestion of TCR-α.
Figure 3
Figure 3
Zinc finger protein 350 spectra: Zinc finger protein 350 was identified in endothelial cells of estrogen receptor negative and not in estrogen receptor-positive breast tissue. LC-Q-TOF MS/MS spectra of LQSESLVNR peptide generated from the trypsin digestion of ZNF 350.
Figure 4
Figure 4
(a) Western blot of ZBRK1 in endothelial cells of estrogen receptor negative (E−) and estrogen receptor positive (E+) breast cancer tissues. (b) Bar diagram showing the relative intensity of ZBRK1 in estrogen receptor negative (E−) and positive (E+) tissues as compared the GAPDH control. ImageJ software was used for densitometric analysis and error bars represents standard error.
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