Song Jin, Jie Chunfa, Polk Paula, Shridhar Ravi, Clair Timothy, Zhang Jun, Yin Lijia, Keppler Daniel
Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, USA.
Biochem Biophys Res Commun. 2006 Feb 3;340(1):175-82. doi: 10.1016/j.bbrc.2005.11.171. Epub 2005 Dec 9.
We recently coined CST6 as a novel candidate tumor suppressor gene for breast cancer. CST6 indeed is expressed in the normal human breast epithelium, but little or not at all in breast carcinomas and breast cancer cell lines. Moreover, ectopic expression of CST6 in human breast cancer cells suppressed cell proliferation, migration, invasion, and orthotopic tumor growth. To obtain insights into the molecular mechanism by which CST6 exhibits its pleiotropic effects on tumor cells, we compared global gene expression profiles in mock- and CST6-transfected human MDA-MB-435S cells. Out of 12,625 transcript species, 61 showed altered expression. These included genes for extracellular matrix components, cytokines, kinases, and phosphatases, as well as several key transcription factors. TaqMan PCR assays were used to confirm the microarray data for 7 out of 11 genes. One down-regulated gene product, secreted autotaxin/lyso-phospholipase D, was of particular interest because its down-regulation by CST6 could explain most of CST6's effect on the breast cancer cells. This study thus provides the first evidence that CST6 plays a role in the modulation of genes, particularly, genes that are highly relevant to breast cancer progression.
我们最近将 CST6 定义为一种新的乳腺癌候选抑癌基因。CST6 在正常人类乳腺上皮细胞中确实有表达，但在乳腺癌组织和乳腺癌细胞系中表达很少或几乎不表达。此外，CST6 在人乳腺癌细胞中的异位表达抑制了细胞增殖、迁移、侵袭以及原位肿瘤生长。为了深入了解 CST6 对肿瘤细胞发挥多效性作用的分子机制，我们比较了空载体转染和 CST6 转染的人 MDA-MB-435S 细胞的全基因组表达谱。在 12625 个转录本中，有 61 个显示表达改变。这些基因包括细胞外基质成分、细胞因子、激酶和磷酸酶的基因，以及几个关键转录因子。TaqMan PCR 分析用于确认 11 个基因中的 7 个基因的微阵列数据。一种下调的基因产物，即分泌型自分泌运动因子/溶血磷脂酶 D，特别引人关注，因为 CST6 对其下调可以解释 CST6 对乳腺癌细胞的大部分作用。因此，这项研究首次证明 CST6 在基因调控中发挥作用，特别是在与乳腺癌进展高度相关的基因调控中。
