EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy.
EpCAM (epithelial cell adhesion molecule) is a cell surface molecule that is known to be highly expressed in colon and other epithelial carcinomas. EpCAM is involved in cell-to-cell adhesion and has been the target of antibody therapy in several clinical trials. To assess the value of EpCAM as a novel target for breast cancer gene therapy, we performed real-time reverse transcription-PCR to quantify the level of EpCAM mRNA expression in normal breast tissue and primary and metastatic breast cancers. We found that EpCAM is overexpressed 100- to 1000-fold in primary and metastatic breast cancer. Silencing EpCAM gene expression with EpCAM short interfering RNA (siRNA) resulted in a 35-80% decrease in the rate of cell proliferation in four different breast cancer cell lines. EpCAM siRNA treatment decreased cell migration by 91.8% and cell invasion by 96.4% in the breast cancer cell line MDA-MB-231 in vitro. EpCAM siRNA treatment was also associated with an increase in the detergent-insoluble protein fraction of E-cadherin, alpha-catenin, and beta-catenin, consistent with the known biology of EpCAM as a regulator of cell adhesion. Our hypothesis is that modulation of EpCAM expression can affect cell migration, invasion, and proliferation by enhancing E-cadherin-mediated cell-to-cell adhesion. These data provide compelling evidence that EpCAM is a potential novel target for breast cancer gene therapy and offer insights into the mechanisms associated with EpCAM gene silencing.
Osta
Walid A
WA
Department of Surgery, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Chen
Yian
Y
Mikhitarian
Kaidi
K
Mitas
Michael
M
Salem
Mohamed
M
Hannun
Yusuf A
YA
Cole
David J
DJ
Gillanders
William E
WE
D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic; D051178:alpha Catenin; D051176:beta Catenin
D000951:Antigens, Neoplasm; C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D000071858:Epithelial Cell Adhesion Molecule; D034741:RNA, Small Interfering; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin