Isolation and characterization of a primary breast epithelium transforming agent

原代乳腺上皮转化剂的分离和表征

• 批准号: 9466988
• 负责人: Gabriele Luca GUSELLA
• 金额: $ 29.97万
• 依托单位: SKINAXIS, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9466988
• 关键词: Antineoplastic Agents; Antiviral Agents; Biotechnology; Breast Cancer Cell; Breast Cancer Patient; Breast Cancer cell line; Breast Cancer therapy; Breast Carcinoma; Breast Epithelial Cells; Breast Feeding; Cells; Centrifugation; Conditioned Culture Media; DNA sequencing; Data; Development; Diagnostic; Electron Microscopy; Endogenous Retroviruses; Epithelial Cells; Epithelium; Etiology; Exposure to; Generations; Genetic; Genetic Materials; Hereditary Breast Carcinoma; Human; Human Herpesvirus 4; Human Milk; Human Papillomavirus; Human papillomavirus 6; In Vitro; Infectious Agent; Inherited; Kidney; Knock-out; Laboratories; Lead; Length; Light; Malignant Neoplasms; Mammary Neoplasms; Mammary gland; Mouse Mammary Tumor Virus; Nature; Oncogenic Viruses; Pathogenesis; Phase; Phenotype; Property; Proteins; Proteomics; RNA-Directed DNA Polymerase; Role; Signal Transduction; Skin; Small Interfering RNA; Speed; Stress; Structure of thyroid parafollicular cell; System; Technology; Testing; Therapeutic; Tissues; Transfection; Tumor Tissue; Tumorigenicity; Vaccines; Validation; Vertical Disease Transmission; Viral; Viral Pathogenesis; Virion; Virus; Woman; base; cell transformation; comparative; in vivo; inhibitor/antagonist; malignant breast neoplasm; malignant phenotype; mammary epithelium; novel diagnostics; particle; prevent; tool; transcriptomics; transforming virus; tumor; tumorigenic; ultraviolet irradiation

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.

摘要 乳腺癌（BC）是女性中最常见的癌症。病毒一直被怀疑 乳腺癌的病因然而，尽管在人BC细胞中鉴定出病毒体， 母乳和许多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BC中得到证实。 我们的初步数据提供了令人信服的证据，证明在一种可过滤的转化剂中存在。 我们在体外建立的BC细胞系的上清液。这种病原体是可传播的， 原代人乳腺上皮细胞在体外，并赋予这些细胞的致瘤表型 in vivo.根据初步结果，我们假设，一种病毒占观察到的人类 乳腺上皮细胞转化活性。 本申请具有分离和表征这种转化的非常集中的目标 采用全面和互补的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，为肿瘤的发病机制提供了新的思路。 重要的是，BC转化病毒的分离将允许开发新的诊断方法。 工具、疫苗和具有重要治疗价值的特异性抑制剂。