Implications of CLSPN Variants in Cellular Function and Susceptibility to Cancer.
Implications of CLSPN Variants in Cellular Function and Susceptibility to Cancer.
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DOI：
10.3390/cancers12092396
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发表时间：
2020-08-24
期刊：
影响因子：
5.2
通讯作者：
Martins TC
中科院分区：
文献类型：
--
作者：
Azenha D;Hernandez-Perez S;Martin Y;Viegas MS;Martins A;Lopes MC;Lam EW;Freire R;Martins TC
Claspin是一种多功能蛋白质，参与细胞稳态所必需的生理过程，这些过程在癌症中通常是有缺陷的，即由于遗传变化。可以想象，Claspin基因（CLSPN）的改变可能有助于癌症的发展。因此，CLSPN生殖系改变的特点是散发性和家族性乳腺癌和神经胶质瘤样品，以及在六个癌细胞系。研究了它们与癌症易感性和功能影响的关系。共发现8种变体（C.- 17G>A、c.1574A>G、c.2230T>C、c.2028+16G>A、c.3595-3597del和c.3839C>T）。CLSPN c.1574A>G（p.Asn525Ser）与乳腺癌显著相关，并分别在小基因剪接测定和信号实验中显示出引起部分外显子跳跃和Claspin表达降低以及Chk 1活化。CLSPN c.2028+ 16 G>A与家族性乳腺癌和神经胶质瘤显著相关，而c.2230 T>C（p.Ser744Pro）仅在乳腺癌和神经胶质瘤患者中检测到，但在健康对照中未检测到。其余的变异与癌症缺乏显著的关联。然而，C- 68 C>T启动子变体在荧光素酶测定中增加转录活性。总之，本研究中鉴定的一些CLSPN变体似乎通过改变CLSPN转录和RNA加工以及Chk 1激活来调节Claspin的功能。
Claspin is a multifunctional protein that participates in physiological processes essential for cell homeostasis that are often defective in cancer, namely due to genetic changes. It is conceivable that Claspin gene (CLSPN) alterations may contribute to cancer development. Therefore, CLSPN germline alterations were characterized in sporadic and familial breast cancer and glioma samples, as well as in six cancer cell lines. Their association to cancer susceptibility and functional impact were investigated. Eight variants were identified (c.-68C>T, c.17G>A, c.1574A>G, c.2230T>C, c.2028+16G>A, c.3595-3597del, and c.3839C>T). CLSPN c.1574A>G (p.Asn525Ser) was significantly associated with breast cancer and was shown to cause partial exon skipping and decreased Claspin expression and Chk1 activation in a minigene splicing assay and in signalling experiments, respectively. CLSPN c.2028+16G>A was significantly associated with familial breast cancer and glioma, whereas c.2230T>C (p.Ser744Pro), was exclusively detected in breast cancer and glioma patients, but not in healthy controls. The remaining variants lacked a significant association with cancer. Nevertheless, the c.-68C>T promoter variant increased transcriptional activity in a luciferase assay. In conclusion, some of the CLSPN variants identified in the present study appear to modulate Claspin’s function by altering CLSPN transcription and RNA processing, as well as Chk1 activation.
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影响因子：
7
作者：
Ke, Shengdong;Shang, Shulian;Chasin, Lawrence A.
通讯作者：
Chasin, Lawrence A.
影响因子：
16.6
作者：
Bianco, Julien N.;Bergoglio, Valerie;Pasero, Philippe
通讯作者：
Pasero, Philippe
影响因子：
4.8
作者：
Jeong, SY;Kumagai, A;Dunphy, WG
通讯作者：
Dunphy, WG
影响因子：
3.8
作者：
Fraile-Bethencourt, Eugenia;Valenzuela-Palomo, Alberto;Velasco, Eladio A.
通讯作者：
Velasco, Eladio A.
DOI：
10.1007/978-1-60761-759-4_15
发表时间：
2010-01-01
期刊：
CANCER SUSCEPTIBILITY: METHODS AND PROTOCOLS
影响因子：
--
作者：
Gaildrat, Pascaline;Killian, Audrey;Tosi, Mario
通讯作者：
Tosi, Mario