Pogo B G, Holland J F, Wang Y, Melana S M, Pelisson I, Liu B, Go V, Bleiweiss I
Department of Medicine, Mount Sinai School of Medicine, New York, USA.
Medicina (B Aires). 1997;57 Suppl 2:75-80.
The participation of viruses in mammary carcinogenesis has been largely studied in animals. A model similar to the mouse mammary tumor virus (MMTV) was previously proposed. Several lines of research supported the participation of MMTV in human breast cancer, but these evidences were contradicted when further research was performed. One major issue was the presence of human endogenous retroviral sequences that confounded results reporting MMTV-like sequences in human breast cancer. To overcome this problem we selected a 660 bp sequence of the MMTV env gene with low homology to endogenous sequences and search for a sequence to it using the polymerase chain reaction (PCR). The sequence was found in 38% of the human breast cancers and in 2% of the normal breasts studied. The sequence was not present in tumors from other organs. It was 90-98% homologous to MMTV and only 18% to human endogenous retrovirus (HERV) K-10. It was also detected in some of the positive tumors by Southern blot hybridization using one of the cloned 660 bp as a probe. Using reverse transcriptase PCR, it was possible to demonstrate that the 660 bp sequence is expressed in the majority of the tumors. Also, preliminary experiments revealed that sequences related to the LTR and gag genes of MMTV were present in the DNA of breast tumors. The origin of the MMTV-like sequences in tumor DNA could be the result of integrated MMTV-like sequences derived from a human mammary virus or may represent unknown endogenous sequences that can only be detected in breast tumors.
病毒在乳腺癌发生中的作用在动物实验中已有大量研究。此前曾提出一种类似于小鼠乳腺肿瘤病毒(MMTV)的模型。多项研究支持MMTV参与人类乳腺癌的发生,但进一步研究时这些证据却相互矛盾。一个主要问题是人类内源性逆转录病毒序列的存在,这使得在人类乳腺癌中报告MMTV样序列的结果受到混淆。为克服这一问题,我们选择了一段与内源性序列同源性较低的MMTV env基因660 bp序列,并使用聚合酶链反应(PCR)寻找与之匹配的序列。在38%的人类乳腺癌和2%的所研究正常乳腺中发现了该序列。在其他器官的肿瘤中未发现该序列。它与MMTV的同源性为90 - 98%,与人类内源性逆转录病毒(HERV)K - 10的同源性仅为18%。使用克隆的660 bp序列之一作为探针,通过Southern印迹杂交在一些阳性肿瘤中也检测到了该序列。使用逆转录酶PCR,可以证明660 bp序列在大多数肿瘤中表达。此外,初步实验表明,乳腺肿瘤DNA中存在与MMTV的LTR和gag基因相关的序列。肿瘤DNA中MMTV样序列的来源可能是源自人类乳腺病毒的整合MMTV样序列的结果,也可能代表仅在乳腺肿瘤中可检测到的未知内源性序列。