Expression of multiple human endogenous retrovirus surface envelope proteins in ovarian cancer.
Individual classes of human endogenous retrovirus (HERV) genes and proteins are expressed in cancer, but expression of more than one type of HERV is rare. We report here the expression of multiple HERV genes and proteins in ovarian cell lines and tissues. Expression of HERV-K env mRNA was greater in ovarian epithelial tumors than in normal ovarian tissues (N = 254). The expression of this protein on the surface and in the cytoplasm of ovarian cancer cells was confirmed using anti-HERV-K specific antibody by flow cytometric analysis. The frequency of expression of HERV-K env protein in multitissue microarrays (N = 641) was determined by immunohistochemistry and a significant correlation with tumor histotype was found. A significantly increased expression of HERV-K was observed in tumors with low malignant potential and low grade, relative to expression in normal ovarian tissues. The increase in expression of HERV-K env protein took place in a stepwise fashion in serous papillary adenocarcinoma. Interestingly, we found that other classes of HERV env mRNAs, including ERV3 and HERV-E, are expressed in the same ovarian cancer tissues that expressed HERV-K. Furthermore, anti-HERV antibodies including anti-ERV3 (30%), anti-HERV-E (40%) and anti-HERV-K (55%) were detected in patients with ovarian cancer, but not in normal female controls. HERV env proteins are frequently transcribed and translated in ovarian epithelial tumors, and multiple HERV families are detectable in ovarian cancer. HERV env proteins, and especially those expressed on the cell surface, may serve as novel tumor targets for detection, diagnosis and immunotherapy of ovarian cancer.
Wang-Johanning
Feng
F
Department of Veterinary Sciences and Michale E. Keeling Center for Comparative Medicine and Research, University of Texas MD Anderson Cancer Center, Houston, TX 78602, USA. fwangjoh@mdanderson.org
Liu
Jinsong
J
Rycaj
Kiera
K
Huang
Miao
M
Tsai
Kate
K
Rosen
Daniel G
DG
Chen
Dung-Tsa
DT
Lu
Danielle W
DW
Barnhart
Kirstin F
KF
Johanning
Gary L
GL
D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000821:virology; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000821:virology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D018269:Carcinoma, Endometrioid / Q000378:metabolism / Q000821:virology; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000821:virology; D020077:Endogenous Retroviruses / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000821:virology; D010053:Ovary / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
D015686:Gene Products, env; D008565:Membrane Proteins; C469430:Np9 protein, HERV-K, human; D012333:RNA, Messenger