کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2152200 | 1090052 | 2008 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Human Endogenous Retrovirus (HERV-K) Reverse Transcriptase as a Breast Cancer Prognostic Marker
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 10, Issue 6, June 2008, Pages 521-533, IN1-IN2
Journal: Neoplasia - Volume 10, Issue 6, June 2008, Pages 521-533, IN1-IN2
نویسندگان
Maya Golan, Amnon Hizi, James H. Resau, Neora Yaal-Hahoshen, Hadar Reichman, Iafa Keydar, Ilan Tsarfaty,