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首页> 外文期刊>Radiation oncology investigations >Molecular and anatomic considerations in the pathogenesis of breast cancer.
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Molecular and anatomic considerations in the pathogenesis of breast cancer.

机译：乳腺癌发病机理的分子和解剖学考虑。

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In spite of the recent recognition of specific genes associated with an elevated lifetime incidence risk of breast cancer, the molecular mechanisms of breast tumor formation remain largely unknown. Tumorigenesis is thought to be highly complex, likely involving the accumulation of 5-10 genetic and epigenetic events. Recent investigations have begun to identify some of these events, and in vitro model systems for breast tumorigenesis, including radiation-induced breast cancer, are expected to provide further insight. Normal human breast epithelial cells exhibit a finite life span, both in vivo and in vitro. A critical event in oncogenic transformation is the ability of cells to multiply indefinitely, a phenomenon referred to as "immortalization." Using human papillomavirus (HPV) oncogenes, multiple normal breast epithelial subtypes have been shown to have distinct susceptibilities to immortalization by the HPV E6 and E7 oncogenes. Because HPV E6 and E7 inactivate two well-known tumor suppressor proteins, p53 and Rb, respectively, this suggests that a cell-type-specific predominance exists with respect to these tumor suppressor pathways. Additional evidence for variability to oncogenic stimuli among normal breast epithelial cells is provided by findings of locally confined loss of heterozygosity. An in vitro model of radiation-induced breast cancer is associated with early abrogation of p53 function. The resultant pair of normal and radiation-transformed breast epithelial cells serves as a useful system to identify other genes critically relevant to breast tumorigenesis. These and other models should help further define the molecular mechanisms underlying the early steps of breast cancer formation.
机译：尽管最近认识到与乳腺癌的终生发病风险升高相关的特定基因，但是乳腺癌形成的分子机制仍然是未知的。肿瘤发生被认为是高度复杂的，可能涉及5-10个遗传和表观遗传事件的积累。最近的研究已经开始确定其中一些事件，并且用于乳腺肿瘤发生的体外模型系统（包括辐射诱发的乳癌）有望提供进一步的见解。正常的人乳房上皮细胞在体内和体外均显示有限的寿命。致癌转化的关键事件是细胞无限增殖的能力，这种现象称为“永生化”。使用人类乳头瘤病毒（HPV）癌基因，已显示多种正常的乳腺上皮亚型对HPV E6和E7癌基因具有永生化的独特敏感性。因为HPV E6和E7分别使两种众所周知的抑癌蛋白p53和Rb失活，所以这表明在这些抑癌途径中存在细胞类型特异性优势。正常局限性上皮细胞杂合性丧失的发现为正常乳腺上皮细胞中致癌性刺激的变异性提供了其他证据。辐射诱发的乳腺癌的体外模型与p53功能的早期废除有关。所得的一对正常的和经辐射转化的乳腺上皮细胞可作为一种有用的系统，用于鉴定与乳腺肿瘤发生极为相关的其他基因。这些模型和其他模型应有助于进一步定义乳腺癌形成早期步骤的分子机制。

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