HUMAN ENDOGENOUS RETROVIRUS-K-ENVELOPE-GENE ENCODED GLYCOPROTEIN, AND A MONOCLONAL ANTIBODY FOR DIAGNOSTIC AND THERAPEUTIC PURPOSES

摘要

The human endogenous retroviral K (HERV-K) genomes have distinct homologies to murine mammary tumor virus which is involved in the genesis of murine breast cancer. By means of a polymerase chain reaction we amplified a 1053 bp DNA segment (nt.6791-7842) from the putative outer membrane part (nt.6733-7842) of the HERV-K-envelope gene. A 959bp (nt.7691-7749) part of the amplified DNA was inserted into the pAX-bacterial-expression-vector. A recombinant fusion protein of a HERV-K-envelope-portion with beta -galactosidase was obtained. A monoclonal antibody was generated which recognizes the envelope portion of the HERV-K-envelope- beta -galactosidase-fusion's protein (FP). This mAB is capable of immunoprecipitating a 67kD glycoprotein from the human breast carcinoma cell line T47D, the amount of which is strongly enhanced after stimulation with estradiol/progesterone. The same band could be precipitated from other carcinoma cell lines (Hep2, MCF7 and HELA), but not from the human B-lymphoblastoid cell line Raji and the mouse myeloma cell line Ag8.653. We interpret these data to suggest that the antigen recognized by the anti-HERV1 mAb is the translational product of an active HERV-K-env gene or whole HERV-K provirus.