Isolation and characterization of a primary breast epithelium transforming agent

摘要 乳腺癌(BC)是女性最常见的癌症。长期以来，人们一直怀疑病毒 作为乳腺癌的原因之一。然而，尽管在人类BC细胞和 母乳和大量研究表明乳腺癌和乳腺癌之间可能存在联系 EB病毒(EBV)、小鼠乳腺肿瘤病毒(MMTV)和人乳头瘤病毒(HPV)， 这些病毒的致瘤潜力尚未在不列颠哥伦比亚省得到证实。 我们的初步数据提供了令人信服的证据，表明可过滤的转化剂存在于 我们在体外建立的BC细胞系的培养上清。这种毒剂是可传播的，可以转化为 原代培养人乳腺上皮细胞，并赋予其致瘤表型 在活体内。根据初步结果，我们假设观察到的人类是由病毒引起的。 乳腺上皮细胞转化活性。 这个应用程序的目标非常集中，就是分离和表征这种转变 采用全面和互补蛋白质组学和转录组学方法的试剂 和体外基因验证系统。这项研究的结果将提供第一个证据 人乳腺上皮细胞转化剂，为肿瘤发病机制提供了新的线索。 重要的是，BC转化病毒的分离将使开发新的诊断方法成为可能 具有显著治疗价值的工具、疫苗和特定的抑制剂。

Abstract Breast cancer (BC) is the most common cancer among women. Viruses have long been suspected as a cause of breast cancer. However, despite the identification of virions in human BC cells and human milk and numerous studies that suggest possible connection between breast cancer and Epstein-Barr virus (EBV), mouse mammary tumor virus (MMTV), and human papilloma virus (HPV), the tumorigenic potential of these viruses has not been proven in BC. Our preliminary data offer the compelling evidence that a filterable transforming agent is present in the supernatant of a BC cell line that we established in vitro. This agent is transmissible, transforms primary human mammary epithelial cells in vitro, and confers these cells the tumorigenic phenotype in vivo. Based on preliminary results, we hypothesize that a virus accounts for the observed human mammary epithelial cells transforming activity. This application has the very focused objective of isolating and characterizing this transforming agent employing comprehensive and complementary proteomics and transcriptomics approaches and in vitro genetic validation systems. The results of this study will provide the first evidence of a human mammary epithelial cells transforming agent and shed new light into tumor pathogenesis. Importantly, the isolation of a BC transforming virus will allow the development of novel diagnostic tools, vaccines, and specific inhibitors of significant therapeutic value.