癌症研究历史经典回顾和热点寻踪（三）
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多细胞生物一个特点是含有来自父本和母本的各一半的基因组，这两种不同来源的遗传信息除了DNA序列有一些差异外，它们的表遗传也很不一样，虽然精子进入卵细胞之后去甲基化等表遗传改变，之后又重新甲基化等表遗传改变，但是该过程与卵细胞的表遗传改变很不一样，这种表遗传的差别是体细胞克隆难以解决的问题，也是动物克隆成功率很低的一个重要原因。The conflict theory of genomic imprinting理论用来解释该现象，现在Stewart CL实验研究表明父本和母本的遗传信息在癌变过程中确实起不同的作用，该实验间接支持The conflict theory of genomic imprinting，最近去年获得美国科学院院士称号的 Jaenisch R发表文章：广泛的基因印记丢失可导致小鼠发生多种肿瘤，该实验与下面该实验似乎相通。
1: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13344-9. Epub 2003 Oct 27.Paternal and maternal genomes confer opposite effects on proliferation, cell-cycle length, senescence, and tumor formation.Hernandez L, Kozlov S, Piras G, Stewart CL.
2: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Loss of imprinting is the silencing of active imprinted genes or the activation of silent imprinted genes, and it is one of the most common epigenetic changes associated with the development of a wide variety of tumors. Here, we have analyzed the effects that global imprinted gene expression has on cell proliferation and transformation. Primary mouse embryonic fibroblasts (MEFs), whose entire genome is either exclusively paternal (androgenetic) or maternal (parthenogenetic), exhibit dramatically contrasting patterns of growth. In comparison with biparental MEFs, andro-genetic proliferation is characterized by a shorter cell cycle, increased saturation density, spontaneous transformation, and formation of tumors at low passage number. Parthenogenetic MEFs reach a lower saturation density, senesce, and die. The maternally expressed imprinted genes p57kip2 and M6P/Igf2r retard proliferation and reduce the long-term growth of MEFs. In contrast, the paternally expressed growth factor Igf2 is essential for the long-term proliferation of all genotypes. Increased Igf2 expression in primary MEFs not only stimulates proliferation, but also results in their rapid conversion to malignancy with tumor formation of short latency. Our results reveal that paternally expressed imprinted genes, in the absence of maternal imprinted genes, predispose fibroblasts to rapid transformation. A potent factor in their transformation is IGF2, which on increased expression results in the rapid conversion of primary cells to malignancy. These results reveal a route by which malignant choriocarcinoma may arise from molar pregnancies. They also suggest that the derivation of stem cells from parthenogenetic embryos, for the purposes of therapeutic cloning, may be ineffective.
非整倍体与癌变关系目前是癌症研究的一个争论焦点，看看目前流行的4个观点：
Nguyen HG, Ravid K.Tetraploidy/aneuploidy and stem cells in cancer promotion: The role of chromosome passenger proteins.J Cell Physiol. 2006 Jul;208(1):12-22. Review.
如果科学的本质只是寻求物质之间的一种关系，而医学或者工程学的本质只是希望找到一种物质可以影响到另一种的物质的学问，那么，关系学和实用学的结合是不是能够更好的指导我们对科学的认识？
编辑：西门吹血
1: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13344-9. Epub 2003 Oct 27.Paternal and maternal genomes confer opposite effects on proliferation, cell-cycle length, senescence, and tumor formation.Hernandez L, Kozlov S, Piras G, Stewart CL.
2: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Loss of imprinting is the silencing of active imprinted genes or the activation of silent imprinted genes, and it is one of the most common epigenetic changes associated with the development of a wide variety of tumors. Here, we have analyzed the effects that global imprinted gene expression has on cell proliferation and transformation. Primary mouse embryonic fibroblasts (MEFs), whose entire genome is either exclusively paternal (androgenetic) or maternal (parthenogenetic), exhibit dramatically contrasting patterns of growth. In comparison with biparental MEFs, andro-genetic proliferation is characterized by a shorter cell cycle, increased saturation density, spontaneous transformation, and formation of tumors at low passage number. Parthenogenetic MEFs reach a lower saturation density, senesce, and die. The maternally expressed imprinted genes p57kip2 and M6P/Igf2r retard proliferation and reduce the long-term growth of MEFs. In contrast, the paternally expressed growth factor Igf2 is essential for the long-term proliferation of all genotypes. Increased Igf2 expression in primary MEFs not only stimulates proliferation, but also results in their rapid conversion to malignancy with tumor formation of short latency. Our results reveal that paternally expressed imprinted genes, in the absence of maternal imprinted genes, predispose fibroblasts to rapid transformation. A potent factor in their transformation is IGF2, which on increased expression results in the rapid conversion of primary cells to malignancy. These results reveal a route by which malignant choriocarcinoma may arise from molar pregnancies. They also suggest that the derivation of stem cells from parthenogenetic embryos, for the purposes of therapeutic cloning, may be ineffective.
非整倍体与癌变关系目前是癌症研究的一个争论焦点，看看目前流行的4个观点：
Nguyen HG, Ravid K.Tetraploidy/aneuploidy and stem cells in cancer promotion: The role of chromosome passenger proteins.J Cell Physiol. 2006 Jul;208(1):12-22. Review.
如果科学的本质只是寻求物质之间的一种关系，而医学或者工程学的本质只是希望找到一种物质可以影响到另一种的物质的学问，那么，关系学和实用学的结合是不是能够更好的指导我们对科学的认识？
编辑：西门吹血
作者: cypress1975
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