Faculty of Science and School of Medical Sciences, School of Biotechnology and Biomolecular Sciences, University of New South Wales, UNSW Sydney, Australia.
Cancer Res. 2010 May 1;70(9):3576-85. doi: 10.1158/0008-5472.CAN-09-4160. Epub 2010 Apr 13.
Mouse mammary tumor virus (MMTV) sequences have been reported to be present in some human breast cancers, but it is unclear whether they have any causal role. In mice, MMTV promotes tumor formation indirectly by insertional mutagenesis of Wnt oncogenes that lead to their activation. In this study, we investigated the status of Wnt-1 in human breast cancers harboring MMTV-like sequences encoding viral envelope (env) genes. We confirmed the detection of env sequences in the nucleus of human breast cancer specimens that are similar in appearance to mouse mammary tumors expressing MMTV env sequences. MMTV env sequences in human breast cancers were also nearly indistinguishable from env sequences in mouse MMTV isolates. Further, Wnt-1 expression was higher in specimens of env-positive ductal carcinoma in situ and invasive ductal carcinoma, relative to env-negative specimens. Our findings extend the evidence that MMTV sequences found in naturally occurring mouse mammary tumors can be found in some human breast cancers, prompting further evaluation of causal roles in these settings.
鼠乳腺肿瘤病毒（MMTV）序列已被报道存在于一些人类乳腺癌中，但尚不清楚它们是否具有任何因果作用。在小鼠中，MMTV 通过插入突变 Wnt 癌基因来促进肿瘤形成，从而导致它们的激活。在这项研究中，我们研究了携带类似 MMTV 包膜（env）基因编码病毒的人类乳腺癌中 Wnt-1 的状态。我们证实了在外观上类似于表达 MMTV env 序列的小鼠乳腺肿瘤的人类乳腺癌标本的核中检测到 env 序列。人类乳腺癌中的 MMTV env 序列也与小鼠 MMTV 分离株中的 env 序列几乎无法区分。此外，与 env 阴性标本相比，env 阳性导管原位癌和浸润性导管癌标本中的 Wnt-1 表达更高。我们的发现扩展了证据，即在自然发生的小鼠乳腺肿瘤中发现的 MMTV 序列也可以在一些人类乳腺癌中找到，促使在这些情况下进一步评估其因果作用。
