Human sterile alpha motif domain 9, a novel gene identified as down-regulated in aggressive fibromatosis, is absent in the mouse.
Human sterile alpha motif domain 9, a novel gene identified as down-regulated in aggressive fibromatosis, is absent in the mouse.
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DOI：
10.1186/1471-2164-8-92
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发表时间：
2007-04-03
期刊：
影响因子：
4.4
通讯作者：
Alman BA
中科院分区：
文献类型：
--
作者：
Li CF;MacDonald JR;Wei RY;Ray J;Lau K;Kandel C;Koffman R;Bell S;Scherer SW;Alman BA
肿瘤可由导致转录失调的突变驱动。在间充质肿瘤、侵袭性纤维瘤病中，消减杂交鉴定出不育α基序结构域9（SAMD9）是肿瘤中显着下调的基因。最近发现 SAMD9 在正常磷血症家族性肿瘤钙质沉着症中发生突变。在本研究中，我们研究了 SAMD9 及其旁系同源基因 SAMD9L 的基因结构和功能，并在多种物种中进行了检查。 SAMD9 位于人类染色体 7q21.2 上，具有头尾方向的旁系同源基因不育 α 基序结构域 9 样 (SAMD9L)。尽管这两个基因都存在于多种物种中，但由于独特的基因组重排，SAMD9 的直系同源物在小鼠谱系中丢失了。 SAMD9 和 SAMD9L 均普遍表达于人体组织中。 SAMD9 在多种与 β-连环蛋白稳定相关的肿瘤中以较低水平表达，例如侵袭性纤维瘤病、乳腺癌和结肠癌。 SAMD9 和 SAMD9L 包含氨基末端 SAM 结构域，但预测的蛋白质结构的其余部分并未表现出与其他已知蛋白质基序的实质同源性。 SAMD9 的假定蛋白质产物定位于细胞质。体外数据显示 SAMD9 负向调节细胞增殖。 SAMD9 在结肠癌细胞系 SW480 中的过度表达可减少移植到免疫缺陷小鼠体内时形成的肿瘤体积。 SAMD9和SAMD9L是一个新的基因家族，在调节细胞增殖和抑制肿瘤表型方面发挥作用。据我们所知，这是第一份关于大鼠中存在但在小鼠中丢失的人类基因的报告，这是由于小鼠特异性重排导致 SAMD9 基因丢失。
Neoplasia can be driven by mutations resulting in dysregulation of transcription. In the mesenchymal neoplasm, aggressive fibromatosis, subtractive hybridization identified sterile alpha motif domain 9 (SAMD9) as a substantially down regulated gene in neoplasia. SAMD9 was recently found to be mutated in normophosphatemic familial tumoral calcinosis. In this study, we studied the gene structure and function of SAMD9, and its paralogous gene, SAMD9L, and examined these in a variety of species. SAMD9 is located on human chromosome 7q21.2 with a paralogous gene sterile alpha motif domain 9 like (SAMD9L) in the head-to-tail orientation. Although both genes are present in a variety of species, the orthologue for SAMD9 is lost in the mouse lineage due to a unique genomic rearrangement. Both SAMD9 and SAMD9L are ubiquitously expressed in human tissues. SAMD9 is expressed at a lower level in a variety of neoplasms associated with β-catenin stabilization, such as aggressive fibromatosis, breast, and colon cancers. SAMD9 and SAMD9L contain an amino-terminal SAM domain, but the remainder of the predicted protein structure does not exhibit substantial homology to other known protein motifs. The putative protein product of SAMD9 localizes to the cytoplasm. In vitro data shows that SAMD9 negatively regulates cell proliferation. Over expression of SAMD9 in the colon cancer cell line, SW480, reduces the volume of tumors formed when transplanted into immune-deficient mice. SAMD9 and SAMD9L are a novel family of genes, which play a role regulating cell proliferation and suppressing the neoplastic phenotype. This is the first report as far as we know about a human gene that exists in rat, but is lost in mouse, due to a mouse specific rearrangement, resulting in the loss of the SAMD9 gene.
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影响因子：
4.4
作者：
Armengol, L;Marquès-Bonet, T;Estivill, X
通讯作者：
Estivill, X
影响因子：
14.9
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Bairoch, A
影响因子：
11.2
作者：
Kong, Y;Poon, R;Alman, BA
通讯作者：
Alman, BA
影响因子：
56.9
作者：
Thanos, CD;Goodwill, KE;Bowie, JU
通讯作者：
Bowie, JU
影响因子：
8.8
作者：
Tejpar S;Li C;Yu C;Poon R;Denys H;Sciot R;Van Cutsem E;Cassiman JJ;Alman BA
通讯作者：
Alman BA