细胞凋亡与癌变的相生相克——肿瘤的发育生物学根源

Homological and Antagonistic Relationship between Apoptosis and Oncogenesis——The Origin of Cancer in Terms of Developmental Biology

早期癌变(prooncogenesis)是肿瘤诊断和防治的最关键时期,却是癌学研究领域中最薄弱的环节.因此,将从发育生物学视角来探索此时期的基本特征.细胞凋亡和癌变两种相互拮抗的功能均源自失控增殖细胞,不过前者是必然本能,而后者是致癌条件下的或然事件.在早期癌变中,它们之间存在复杂的"相生相克"关系:一方面,开始癌变的细胞尚未累积出足够的致癌基因变异,原发癌的出现尚需不断阻止凋亡功能的监控;另一方面,凋亡功能虽遭到促癌变因子的阻遏,但促凋亡基因,特别是p53尚未发生突变,逆转的可能性仍然存在,因此在防治上有很大的空间.为了给深入探索早期癌变问题提供理论依据,提出了一个"细胞凋亡转向癌变"的假说,初步进行了分子和线粒体生理水平的论证,并强调在癌学研究上如欲获得重大突破,就应以早期癌变为重中之重,同时建议把弄清楚Ca2+以及H+,ROS等荷电粒子的代谢动态作为切入点.

The prooncogenic phase of transforming cells is the critical period wherein the early diagnosis,prevention and cure of cancers could have been effectively executed. clear among all the phases of cancer progress. Therefore, we attempt phase in terms of developmental biology. Arising homologically from Unfortunately, to explore the it remains the least basic nature of this proliferating cells out of control,apoptosis and carcinogenesis, two opposite functions, fight each other intensely in the prooncogenic phase, where the former is an instinctive function, while the latter an unexpeeted contingency caused by procancerous factors. On the one hand, though the progress of oncogenesis has already started, the primary cancers will not emerge until the accumulation of alterations of genes for carcinogenesis is sufficient. And the result is sorely depends on whether the transforming cells could escape successively from the surveillance of apoptosis wherever existing therein; on the other hand, the apoptotic function though has temporarily been arrested by procancerous factors, the lose-function-mutation of proapoptotic genes, mainly p53, has not occurred yet, and committing suicide of transforming cells is still possible. Therefore, there is plenty of room for developing new approaches to control this lethal disease. To encourage a deep exploration of the nature of prooncogenesis, here, we propose a hypothesis about the transorientation of apoptosis towards oncoge-nesis, make a preliminary analysis based on molecular biology and mitochondrial physiology, and strongly recommend that researchers in this field choose the nature of prooncogenesis as their target of first priority and try to make breakthroughs via tackling the metabolism of Ca^2＋, H^＋ and ROS.