Wang Y, Pelisson I, Melana S M, Holland J F, Pogo B G
Mechanism of Disease Therapy Program, Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Int J Oncol. 2001 May;18(5):1041-4. doi: 10.3892/ijo.18.5.1041.
We have previously reported, using the polymerase chain reaction (PCR), the presence of a 660 bp sequence homologous to the env gene of MMTV in 38% of the human breast cancers studied, but not in normal breasts nor in other tumors or tissues. We have now investigated the presence of MMTV-like LTR sequences in human breast cancer and normal breast tissue. Primers were selected to amplify a 630 bp sequence homologous to MMTV, but not to the endogenous retrovirus HERV-K10. This sequence was detected in 41.5% of the breast cancers and none of the normal breasts. A larger 1.2 kb LTR fragment was also amplified with high homology to MMTV. Finally, a 1.6 kb fragment containing env and LTR sequences was amplified, cloned and sequenced from breast cancer DNA. The human LTRs were highly homologous to MMTV contain enhancer and promoter elements, the glucocorticoid responsive element (GRE) and the superantigen (Sag) sequences. Presence of functional sequences implies involvement in transcriptional regulation, whereas presence of an env-LTR sequence indicates contiguity within the genome of a potential provirus. Their presence in breast cancer DNA, but not in normal tissue, suggest an exogenous origin.
我们之前曾报道，利用聚合酶链反应（PCR），在所研究的38%的人类乳腺癌中存在与小鼠乳腺肿瘤病毒（MMTV）env基因同源的660 bp序列，但在正常乳腺组织、其他肿瘤或组织中未发现。我们现在研究了人类乳腺癌和正常乳腺组织中类MMTV长末端重复序列（LTR）的存在情况。选择引物以扩增与MMTV同源但与内源性逆转录病毒HERV-K10不同源的630 bp序列。在41.5%的乳腺癌中检测到该序列，而在所有正常乳腺组织中均未检测到。还扩增出了一个与MMTV具有高度同源性的更大的1.2 kb LTR片段。最后，从乳腺癌DNA中扩增、克隆并测序了一个包含env和LTR序列的1.6 kb片段。人类LTR与MMTV高度同源，包含增强子和启动子元件、糖皮质激素反应元件（GRE）和超抗原（Sag）序列。功能序列的存在意味着参与转录调控，而env-LTR序列的存在表明潜在前病毒基因组内的连续性。它们存在于乳腺癌DNA中，而不存在于正常组织中，提示其来源于外源性。
