Ligand-directed retroviral targeting of human breast cancer cells.
We explored the feasibility of designing retroviral vectors that can target human breast cancer cells with characteristic receptors via ligand-receptor interaction. The ecotropic Moloney murine leukemia virus envelope was modified by insertion of sequences encoding human heregulin. Ecotropic virus, which normally does not infect human cells, when pseudotyped with the modified envelope protein now crosses species to infect human breast cancer cell lines that overexpress HER-2 (human epidermal growth factor receptor; also called ERBB2) and HER-4 (also called ERBB4), while human breast cancer cell lines expressing low levels of these receptors remain resistant to infection. Since about 20% of human breast cancers overexpress HER-2 and some of breast cancer cell lines overexpress both HER-2 and HER-4, cell-specific targeting of retroviral vectors may provide a different approach for in vivo gene therapy of this type of breast cancer.
Han
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X
Department of Laboratory Medicine, University of California, San Francisco 94143-0724, USA.
Kasahara
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N
Kan
Y W
YW
D001943:Breast Neoplasms; D002352:Carrier Proteins / Q000235:genetics; D003001:Cloning, Molecular; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D018390:Gene Targeting; D005822:Genetic Vectors / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D008979:Moloney murine leukemia virus / Q000235:genetics*; D020890:Neuregulin-1; D020880:Neuregulins; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D066247:Receptor, ErbB-4; D011993:Recombinant Fusion Proteins; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
D002352:Carrier Proteins; D066246:ErbB Receptors; D006023:Glycoproteins; D020890:Neuregulin-1; D020880:Neuregulins; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C087230:heregulin beta1; C587689:ERBB4 protein, human