Targeted inhibition of EG-1 blocks breast tumor growth.
EG-1 is a gene product that is significantly elevated in human breast cancer tissues. Previously, we have shown that EG-1 overexpression stimulates cellular proliferation both in vitro and in vivo. Here, we ask whether this molecule can be targeted for experimental therapeutic purpose. siRNA lentivirus and polyclonal antibodies were designed to suppress EG-1 expression. These agents were then used in cell culture proliferation assays and breast tumor xenograft models. Serum and urine from breast cancer patients were also analyzed for the presence of EG-1 peptide. We report here for the first time that endogenous EG-1 can be targeted to inhibit breast tumor growth. This inhibition, whether delivered via siRNA lentivirus or polyclonal antibody, resulted in decreased cellular proliferation in culture and smaller xenografts in mice. The effects were shown in both ER (estrogen receptor)-positive human breast cancer MCF-7 cells, as well as in ER-negative MDA-MB-231 cells. Furthermore, we detected soluble EG-1 in serum and urine of breast cancer patients. These observations demonstrate that EG-1 is relevant to human breast cancer, and is a molecular target worthy of translational efforts into effective breast cancer therapy.
Lu
Ming
M
University of California, Los Angeles School of Medicine, Department of Surgery, Division of Oncology, Los Angeles, California, USA.
Sartippour
Maryam R
MR
Zhang
Liping
L
Norris
Andrew J
AJ
Brooks
Mai N
MN
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D056892:Mediator Complex; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism
C496877:MED28 protein, human; D056892:Mediator Complex; D011506:Proteins; D034741:RNA, Small Interfering