Human endogenous retrovirus (HERV-K) reverse transcriptase as a breast cancer prognostic marker.
A reverse transcriptase (RT) cDNA, designated HERV-K-T47D-RT, was isolated from a hormonally treated human breast cancer cell line. The protein product putative sequence is 97% identical to the human endogenous HERV-K retroviral sequences. Recombinant T47D-RT protein was used to generate polyclonal antibodies. The expression of HERV-K-T47D-RT protein increased in T47D cells after treatment with estrogen and progesterone. The RT-associated DNA polymerase activity was substantially increased after over-expressing a chimeric YFP-HERV-K-T47D-RT protein in cells. This RT-associated polymerase activity was significantly reduced by mutating the active site sequence YIDD to SIAA. Moreover, the endogenous RT activity observed in T47D cells was decreased by HERV-K-T47D-RT-specific siRNA, confirming the dependence of the endogenous enzymatic activity. To assess HERV-K-T47D-RT expression in human breast tumors, 110 paraffin sections of breast carcinoma biopsies were stained and subjected to confocal analysis. Twenty-six percent (28/110) of the tumor tissues and 18% (15/85) of the adjacent normal tissue, from the same patients, expressed the RT. HERV-K-T47D-RT expression significantly correlates with poor prognosis for disease-free patients and their overall survival. These results imply that HERV-K-T47D-RT might be expressed in early malignancy and might serve as a novel prognostic marker for breast cancer. Furthermore, these results provide evidence for the possible involvement of endogenous retrovirus in human breast carcinoma.
Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Maya
M
Golan
Amnon
A
Hizi
James H
JH
Resau
Neora
N
Yaal-Hahoshen
Hadar
H
Reichman
Iafa
I
Keydar
Ilan
I
Tsarfaty
D001665:Binding Sites; D014408:Biomarkers, Tumor; D001706:Biopsy; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000821:virology; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D020077:Endogenous Retroviruses / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018613:Microscopy, Confocal; D009154:Mutation; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry
D014408:Biomarkers, Tumor; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D012194:RNA-Directed DNA Polymerase