Human APC2 localization and allelic imbalance.
Human APC2 localization and allelic imbalance.
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发表时间：
2001-11
期刊：
影响因子：
11.2
通讯作者：
C. Jarrett;J. Blancato;T. Cao;D. Bressette;M. Cepeda;P. Young;C. King;S. Byers
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文献类型：
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作者：
C. Jarrett;J. Blancato;T. Cao;D. Bressette;M. Cepeda;P. Young;C. King;S. Byers
第二个腺瘤性结肠息肉病（APC）样基因，APC 2/APCL，最近被描述和定位于19号染色体。我们已经将APC 2精细定位到染色体19p13.3的一个小区域，该区域包含标记D19 S883和WI-19632，该区域通常在各种癌症中丢失，特别是卵巢癌。间期荧光原位杂交分析显示，APC 2等位基因的不平衡在19 20卵巢癌筛选，表明APC 2可能是一个潜在的卵巢癌抑癌基因。当在表达低水平APC 2的SKOV 3卵巢癌细胞中过表达时，外源APC 2定位于高尔基体、含肌动蛋白的结构，偶尔定位于微管。针对人APC 2的NH 2末端的抗体显示内源性APC 2弥散分布在细胞质中，并且与高尔基体和肌动蛋白丝共定位。在用肌动蛋白破坏剂细胞松弛素D处理后，APC 2仍然与肌动蛋白丝结合。这些结果表明，APC 2参与肌动蛋白相关事件，并可能通过与肌动蛋白丝的相互作用影响细胞运动或粘附，以及独立或与APC合作下调β-连环蛋白信号。
A second adenomatous polyposis coli (APC)-like gene, APC2/APCL, was recently described and localized to chromosome 19. We have fine mapped APC2 to a small region of chromosome 19p13.3 containing markers D19S883 and WI-19632, a region commonly lost in a variety of cancers, particularly ovarian cancer. Interphase fluorescence in situ hybridization analysis revealed an APC2 allelic imbalance in 19 of 20 ovarian cancers screened and indicates that APC2 could be a potential tumor suppressor gene in ovarian cancer. When overexpressed in SKOV3 ovarian cancer cells, which express low levels of APC2, exogenous APC2 localized to the Golgi apparatus, actin-containing structures, and occasionally to microtubules. Antibodies against the NH2 terminus of human APC2 show that endogenous APC2 is diffusely distributed in the cytoplasm and colocalizes with both the Golgi apparatus and actin filaments. APC2 remained associated with actin filaments after treatment with the actin-disrupting agent, cytochalasin D. These results suggest that APC2 is involved in actin-associated events and could influence cell motility or adhesion through interaction with actin filaments, as well as functioning independently or in cooperation with APC to down-regulate beta-catenin signaling.