Landscaping the cancer terrain
Landscaping the cancer terrain
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DOI：
10.1126/science.280.5366.1036
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发表时间：
1998-05-15
期刊：
影响因子：
56.9
通讯作者：
Vogelstein, B
中科院分区：
文献类型：
--
作者：
Kinzler, KW;Vogelstein, B
很少有研究比遗传性肿瘤易感综合征的研究更能让我们了解癌症。最初，这些疾病的突变被认为是以直接的方式促进恶性肿瘤，通过“肿瘤抑制”基因的失活，直接调节细胞出生或细胞死亡。然而，最近，通过不太直接的机制起作用的易感基因已经被发现。例如，青少年息肉病综合征（JPS）患者中的基因缺陷--其中之一在本期的第1086页（1）中描述--阐明了这一原理，并且还提出了关于肿瘤细胞与共同构成肿瘤块的“其他细胞”之间关系的基本问题。VHL和APC。这些基因的失活直接导致肿瘤的恶性生长;因此，它们通常起着“守门人”的作用，以防止失控的生长（见图）。因此，对癌细胞缺失的看门人功能的恢复导致肿瘤生长的抑制。
Few lines of investigation have taught us more about cancer than the study of inherited tumor susceptibility syndromes. Initially, the mutations responsible for these diseases were thought to promote malignancy in a straightforward manner, through inactivation of “tumor suppressor” genes, which directly modulate cell birth or cell death. More recently, however, susceptibility genes that work through less-direct mechanisms have come to light. The genes defective in patients with juvenile polyposis syndromes (JPSs), for example—one of which is described on page 1086 of this issue (1)—illuminate this principle and also raise fundamental questions about the relation between neoplastic cells and the “other cells” that together constitute a tumor mass.A dozen tumor suppressor genes are known to prevent cancer through direct control of cell growth—including p53, Rb, VHL, and APC. Inactivation of these genes contributes directly to the neoplastic growth of the tumor; thus, they normally function as “gatekeepers” to prevent runaway growth (see the figure). Accordingly, restoration of the missing gatekeeper function to cancer cells leads to suppression of the neoplastic growth.