BREAST CANCER ETIOLOGY, DETECTION, AND TREATMENT

人类内源性逆转录病毒K型（HERV-K），目前约有50 在基因组中的拷贝，似乎是一个完整的逆转录病毒与开放 阅读框编码gag、pol和env蛋白， 阅读框编码一个假定的调节蛋白。我们一直 研究HERV-K与人类乳腺癌的可能关联 这主要是由于它与小鼠乳腺肿瘤病毒同源， 小鼠乳腺癌。使用新型短期乳腺癌细胞 株，我们已经检查了HERV-K mRNA的表达， RT-PCR和北方印迹法 并观察到所有病毒基因的表达。此外一些 乳腺癌细胞株表现出逆转录病毒RT活性， 灵敏的PCR增强测定。这种活性是否由HERV-K编码 仍有待确定。我们检查了 乳腺肿瘤和匹配的正常邻近组织中的新型HERV-K 整合位点和改变的DNA甲基化模式， 提示HERV-K表达也可能导致 邻近细胞癌基因的表达。一个HERV-K相关的DNA片段 在乳腺肿瘤标本中观察到，但在来自同一组织的正常DNA中没有。 目前正在克隆一个人，并可能证明作为探针有用， 其他乳腺肿瘤中的HERV-K相关性。作为附加 为了研究HERV-K与乳腺癌的关系，我们检查了 基于肽的HERV-K gag和包膜抗原抗体血清 酶联免疫吸附测定。初步研究显示， 突尼斯乳腺癌患者血清中的抗体反应性， 一种非常具有侵袭性的疾病，类似于炎症性乳腺癌， 普遍存在。目前，对从女性获得的编码血清样本的研究 不同类型和阶段的乳腺癌患者 为了验证HERV-K是否与特定的 乳腺癌这些信息不仅可以将内源性病毒 但也可能导致简单诊断的发展， 试验.

The human endogenous retrovirus type K(HERV-K), present at about fifty copies in the genome, appears to be a complete retrovirus with open reading frames encoding gag, pol, and env proteins and a central open reading frame encoding a putative regulatory protein. We have been investigating a possible association of HERV-K with human breast cancer largely due to its homology with mouse mammary tumor virus which causes mammary cancer in mice. Using novel short- term breast cancer cell strains, we have examined HERV-K mRNA expression by reverse transcriptase- polymerase chain reaction (RT-PCR) and northern blotting and have observed expression of all viral genes. In addition, some breast tumor cell strains exhibited retroviral RT activity by a highly sensitive PCR-enhanced assay. Whether this activity is encoded by HERV-K remains to be determined. We have examined paired tissue specimens of breast tumor and matched normal adjacent tissue for novel HERV-K integration sites and altered DNA methylation patterns which might suggest a mechanism whereby expression of HERV-K could also lead to expression of adjacent cellular oncogenes. A HERV-K-related DNA fragment seen in a breast tumor specimen but not in normal DNA from the same individual is currently being cloned and may prove useful as a probe for further HERV-K associations in other breast tumors. As an additional probe for a HERV-K-breast cancer association, we have examined patient sera for antibodies to HERV-K gag and envelope antigens in peptide-based enzyme-linked immunosorbent assays. Preliminary studies showed greater antibody reactivity in sera from breast cancer patients in Tunisia where very aggressive disease resembling inflammatory breast cancer is prevalent. Currently, studies on coded serum samples obtained from women in the U.S. with breast cancers of different types and stages are being carried out in order to verify if HERV-K is associated with a particular breast cancer. This information not only could link the endogenous virus with the cancer, but could also lead to development of simple diagnostic tests.