BREAST CANCER ETIOLOGY, DETECTION, AND TREATMENT

人类基因组包含许多内源性逆转录病毒成分， 尽管大多数似乎是有缺陷的。人类内源性逆转录病毒 然而，K型(Herv-K)在基因组中存在大约50个拷贝， 似乎已经完成了。它拥有开放的阅读框架，可以阅读常见的 Gag、Poll和env逆转录病毒基因，以及中央开放阅读 编码一种假定的调节蛋白的框架。我们一直在 探讨HERV-K在人乳腺癌中的可能作用 在很大程度上取决于Herv-K与HERV-K的显著序列同源性 引起小鼠乳腺癌的小鼠乳腺肿瘤病毒。vbl.使用 新的短期乳腺癌细胞株，我们之前检查过 HERV-K基因的mRNA表达及其在某些配对中的观察 来自人类患者的样本，所有的Herv-K基因都表达了 在来源于肿瘤细胞的培养中，而不是在培养中 来源于匹配的正常邻近组织。此外，一些乳房 肿瘤细胞株表现出逆转录病毒逆转录酶活性， 这不能归因于已知的细胞DNA聚合酶，如 作为DNA聚合酶或其他污染性逆转录酶 动物逆转录病毒。目前我们正在检测其基因的表达。 乳腺肿瘤和正常乳腺组织标本中HERV-K基因的表达 用Northern印迹和反向杂交检测相邻组织 转录酶-聚合酶链式反应以确定是否 完整的HERV-K逆转录病毒在一些人类乳腺癌中表达。 此外，我们正在探索相同的DNA甲基化模式 成对的样本。诱发乳腺癌的一种机制是 涉及甲基化状态的改变，这可能导致表达 HERV-K基因和邻近的细胞癌基因。鉴定 相邻基因的相互作用可能有助于阐明肿瘤的发病机制 归纳法。检测到的逆转录酶活性的性质 也在调查中，以确定它是否由 HERV-K最后，血清学研究仍在继续，以便 确定HERV-K蛋白的表达是否会诱导 某些类型乳房患者的HERV-K特异性抗体 癌症，但不是健康的女性。检测到这种抗体可能会 不仅将特定的癌症与内源性逆转录病毒联系起来，而且 它还可能为初诊或复发提供一种简单的测试。

The human genome contains numerous endogenous retroviral elements, although most appear to be defective. The human endogenous retrovirus type K (HERV-K), however, present at about fifty copies in the genome, appears to be complete. It possesses open reading frames for the usual gag, pol, and env retroviral genes, as well as a central open reading frame which encodes a putative regulatory protein. We have been investigating a possible role of HERV-K in human breast carcinoma based in large part on the significant sequence homology of HERV-K with the mouse mammary tumor virus, which causes mammary cancer in mice. Using novel short-term breast cancer cell strains, we previously examined mRNA expression of HERV-K genes and observed that in some paired samples, derived from human patients, all HERV-K genes were expressed in the culture derived from the tumor cells but not in the culture derived from matched normal adjacent tissue. In addition, some breast tumor cell strains exhibited retroviral reverse transcriptase activity, which could not be attributable to known cellular DNA polymerases, such as DNA polymerase or other contaminating reverse transcriptases from animal retroviruses. Currently we are examining mRNA expression of HERV-K genes in paired tissue samples from breast tumor and normal adjacent tissue by both northern blot and reverse transcriptase-polymerase chain reaction in order to determine if the complete HERV-K retrovirus is expressed in some human breast cancers. In addition, we are exploring DNA methylation patterns in the same paired samples. One mechanism for breast cancer induction could involve altered methylation states, which could lead to expression of HERV-K genes along with adjacent cellular oncogenes. Identification of the adjacent genes could shed light on the mechanism of tumor induction. The nature of the reverse transcriptase activity detected is also under investigation in order to determine if it is encoded by HERV-K. Finally, serologic studies are continuing in order to determine if expression of HERV-K proteins leads to elicitation of HERV-K-specific antibodies in patients with certain types of breast cancer but not in healthy women. Detection of such antibodies could not only link the particular cancer with the endogenous retrovirus, but it might also provide a simple test for initial diagnosis or relapse.