Alteration in protein expression in estrogen receptor alpha-negative human breast cancer tissues indicates a malignant and metastatic phenotype.
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.
Sahab
Ziad J
ZJ
Department of Chemistry and Biochemistry, Institute of Molecular Biophysics, Florida State University, Tallahassee, 32306-4390, USA.
Man
Yan-Gao
YG
Semaan
Suzan M
SM
Newcomer
Robert G
RG
Byers
Stephen W
SW
Sang
Qing-Xiang Amy
QX
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D010641:Phenotype; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D047628:Estrogen Receptor alpha