Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis.
Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis.
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DOI：
10.1186/1471-2407-10-562
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发表时间：
2010-10-18
期刊：
影响因子：
3.8
通讯作者：
Amaar YG
中科院分区：
文献类型：
--
作者：
Reeves ME;Baldwin SW;Baldwin ML;Chen ST;Moretz JM;Aragon RJ;Li X;Strong DD;Mohan S;Amaar YG
Ras相关结构域家族1（RASSF 1）基因是编码两种主要mRNA形式RASSF 1A和RASSF 1C的Ras效应子，其通过选择性启动子选择和选择性mRNA剪接而衍生。RASSF 1A是一个肿瘤抑制基因。然而，关于RASSF 1C在正常和转化细胞中的功能知之甚少。使用基因沉默和过表达技术来调节人乳腺癌细胞中RASSF 1C的表达。使用过表达RASSF 1C的T47 D细胞进行Affymetrix微阵列分析以鉴定RASSF 1C靶基因。RT-PCR和Western blot技术用于验证目的基因的表达。还进行了细胞侵袭和凋亡测定。在这篇文章中，我们报告了改变RASSF 1C在人乳腺癌细胞中表达的影响。我们发现在乳腺癌细胞系（MDA-MB 231和T47 D）中沉默RASSF 1C mRNA导致细胞增殖的小但显著的降低。相反，乳腺癌细胞（MDA-MB 231和T47 D）中RASSF 1C的诱导型过表达导致细胞增殖的小幅增加。我们还报告了新的RASSF 1C靶基因的鉴定。RASSF 1C在乳腺癌细胞中下调几个促凋亡和肿瘤抑制基因，上调几个生长促进基因。我们进一步表明，通过过度表达RASSF 1C下调caspase 3降低了乳腺癌细胞对凋亡诱导剂依托泊苷的敏感性。此外，我们发现RASSF 1C过表达增强T47 D细胞体外侵袭/迁移。总之，我们的研究结果表明，RASSF 1C与RASSF 1A不同，不是肿瘤抑制因子，而是可能在刺激乳腺癌细胞的转移和存活中发挥作用。
The Ras association domain family 1 (RASSF1) gene is a Ras effector encoding two major mRNA forms, RASSF1A and RASSF1C, derived by alternative promoter selection and alternative mRNA splicing. RASSF1A is a tumor suppressor gene. However, very little is known about the function of RASSF1C both in normal and transformed cells. Gene silencing and over-expression techniques were used to modulate RASSF1C expression in human breast cancer cells. Affymetrix-microarray analysis was performed using T47D cells over-expressing RASSF1C to identify RASSF1C target genes. RT-PCR and western blot techniques were used to validate target gene expression. Cell invasion and apoptosis assays were also performed. In this article, we report the effects of altering RASSF1C expression in human breast cancer cells. We found that silencing RASSF1C mRNA in breast cancer cell lines (MDA-MB231 and T47D) caused a small but significant decrease in cell proliferation. Conversely, inducible over-expression of RASSF1C in breast cancer cells (MDA-MB231 and T47D) resulted in a small increase in cell proliferation. We also report on the identification of novel RASSF1C target genes. RASSF1C down-regulates several pro-apoptotic and tumor suppressor genes and up-regulates several growth promoting genes in breast cancer cells. We further show that down-regulation of caspase 3 via overexpression of RASSF1C reduces breast cancer cells' sensitivity to the apoptosis inducing agent, etoposide. Furthermore, we found that RASSF1C over-expression enhances T47D cell invasion/migration in vitro. Together, our findings suggest that RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
30.8
作者：
Dammann, R;Li, C;Pfeifer, GP
通讯作者：
Pfeifer, GP
影响因子：
8
作者：
Dammann, R;Takahashi, T;Pfeifer, GP
通讯作者：
Pfeifer, GP
影响因子：
6.2
作者：
Amaar, YG;Baylink, DJ;Mohan, S
通讯作者：
Mohan, S
影响因子：
--
作者：
Iglesias, Daniel;Fernández-Peralta, Antonia M.;González-Aguilera, Juan J.
通讯作者：
González-Aguilera, Juan J.