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.
Golan
Maya
M
Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Hizi
Amnon
A
Resau
James H
JH
Yaal-Hahoshen
Neora
N
Reichman
Hadar
H
Keydar
Iafa
I
Tsarfaty
Ilan
I
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