BREAST CANCER ETIOLOGY, DETECTION, AND TREATMENT

人类内源性K型逆转录病毒(HERV-K)，目前约有50 在基因组中复制，似乎是一个开放的完整的逆转录病毒 编码Gag、Pol和env蛋白的阅读框架和中央开放 编码一个假定的调节蛋白的阅读框架。我们一直在 研究HERV-K与人类乳腺癌的可能关联 这在很大程度上是因为它与小鼠乳腺肿瘤病毒同源，后者导致 小鼠的乳腺癌。利用新型短期乳腺癌细胞 我们用逆转录方法检测了Herv-K基因的表达 逆转录聚合酶链式反应和Northern印迹 并观察到所有病毒基因的表达。此外，还有一些 乳腺肿瘤细胞株表现出高度的逆转录病毒RT活性 灵敏的聚合酶链式反应增强试验。此活动是否由HERV-K编码 仍有待确定。我们已经检查了成对的组织样本 乳腺肿瘤和匹配的正常邻近组织检测新的HERV-K 整合位点和改变的DNA甲基化模式可能 提示一种机制，即Herv-K的表达也可能导致 相邻细胞癌基因的表达。一个与Herv-K相关的DNA片段 在乳腺肿瘤标本中可见，但在正常DNA中未见 个人目前正在被克隆，并可能被证明是有用的探针 HERV-K在其他乳腺肿瘤中的进一步相关性。作为额外的 HERV-K乳腺癌协会的探索，我们已经检查了患者 多肽中抗Herv-K Gag和包膜抗原抗体的血清 酶联免疫吸附试验。初步研究表明， 突尼斯乳腺癌患者血清中抗体的反应性 类似于炎症性乳腺癌的侵袭性疾病 很流行。目前，对从女性获得的编码血清样本的研究 在美国，不同类型和不同阶段的乳腺癌患者 以验证HERV-K是否与特定的 乳腺癌。这一信息不仅可以将内源性病毒 与癌症有关，但也可能导致制定简单的诊断 测试。

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.