Alteration in protein expression in estrogen receptor alpha-negative human breast cancer tissues indicates a malignant and metastatic phenotype

作者：Sahab, Ziad J.; Man, Yan-Gao; Semaan, Suzan M.; Newcomer, Robert G.; Byers, Stephen W.; Sang, Qing-Xiang Amy^*

来源：Clinical & Experimental Metastasis, 2010, 27(7): 493-503.

DOI：10.1007/s10585-010-9338-8

• Apoptosis
• Cancer heterogeneity
• Estrogen receptor
• Human breast cancer
• Invasion
• Metastasis suppressor
• Mass spectrometry
• Protein biomarker
• Proteomics
• Tumor progression

Ductal carcinoma in situ (DCIS) represents the earliest identifiable breast cancer lesion. Disruption of the myoepithelial cell layer and basement membrane is a prerequisite for DCIS to initiate invasion into the stroma. The majority of epithelial cells overlying a focally-disrupted myoepithelial cell layer are estrogen receptor-alpha negative (ER(-)); however, adjacent cells within the same duct confined by an intact myoepithelial cell layer express high levels of ER. These ER (+) and ER (-) cells were microdissected from the same ducts of breast cancer patients. Differential proteins expressed by ER(+) and ER(-) cells were identified using two-dimensional gel electrophoresis followed by mass spectrometry and Western blot analysis. ER(-) cells express lower levels of superoxide dismutase, RalA binding protein, galectin-1, uridine phosphorylase 2, cellular retinoic acid-binding protein 1, S100 calcium binding protein A11, and nucleoside diphosphate kinase A or non-metastasis protein 23-H1 (nm23-H1). The upregulated protein, Rho GDP-dissociation inhibitor 1 alpha, may induce chemotherapy resistance. The significant findings are that the microdissected ER(-) cells express 12.6 times less cellular retinoic acid-binding protein 1, a protein involved in cellular differentiation, and 4.1 times less nucleoside diphosphate kinase A or nm23-H1, a metastasis suppressor, and express fewer proteins than adjacent ER(+) cells. The collective role of the alterations of protein expression in ER(-) cells may be to promote a more malignant phenotype than adjacent ER(+) cells, including a decreased ability to undergo apoptosis and differentiation, and an increased potential to damage DNA, metastasize, and resist to chemotherapy.

• 出版日期2010-10
• 单位吉林大学