Role of the p53 homolog p73 in cancer

主要研究者/项目负责人（最后，第一，中间）：Moll，Ute，M p63和p73在癌症中的作用 PI：Ute M. Moll，医学博士 摘要 p53控制强大的应激反应，是典型的肿瘤抑制因子。p63的发现， p73是p53家族中的两个成员，引起了人们对其个体和集体功能的许多猜测。 然而，尽管存在强烈的共识，即这两种基因在癌症中起主要作用，但目前的数据表明， 它们的性质是否是肿瘤抑制性的、致癌的或在某些情况下两者都是矛盾的。虽然他们的 从基因切除研究中可以立即看出它们在发育中的作用， 由于缺乏人类和小鼠的明确遗传数据，癌症仍然难以捉摸。由于第二次内部 启动子和选择性剪接，p63和p73是复杂的双极基因，产生多种亚型， 可以简单地看作是 两种对立基因合二为一.此外，与无处不在的 p53、p63和p73的突变改变的特征在于实际上不存在失活突变， 而是在肿瘤中表现出特异性同种型的异常表达。 该基金旨在阐明这两种基因在特定致癌背景下的体内作用， 基于两个前提。首先，正常组织在其组织类型和亚型方面表现出惊人的特异性。 p63和p73的表达，一个重要的事实，到目前为止很少受到关注，但可能持有的，

Principal Investigator/Program Director (Last, first, middle): Moll, Ute, M Title: the Role of p63 and p73 in Cancer PI: Ute M. Moll, M.D. Abstract p53 controls a powerful stress response and is a quintessential tumor suppressor. The discovery of p63 and p73, two p53 family members, provoked much speculation about their individual and collective functions. However, while a strong consensus exists that both genes play a major role in cancer, current data is conflicting whether their nature is tumor suppressive, oncogenic or in some context both. Although their function in development was immediately apparent from gene ablation studies, delineating their exact role in cancer remains elusive due to a lack of clear genetic data in humans and mice. Due to a second internal promoter and alternative splicing, p63 and p73 are complex bipolar genes giving rise to multiple isoforms that can simplistically be viewed as Two Opposing-Genes-in-One. Moreover, in sharp contrast to the ubiquitous mutational alteration of p53, p63 and p73 are characterized by a virtual absence of inactivating mutations, and instead exhibit aberrant expression of specific isoforms in tumors. This grant aims at elucidating the in vivo role of both genes in specific oncogenic contexts and is based on two premises. First, normal tissues exhibit a striking specificity for tissue types and isoforms in their p63 and p73 expression, an important fact that up to now received little attention, yet likely holds the