Cornmark Louise, Lønne Gry Kalstad, Jögi Annika, Larsson Christer
Center for Molecular Pathology, Lund University, Skåne University Hospital, Entrance 78, 3rd floor, 205 02, Malmö, Sweden.
Tumour Biol. 2011 Oct;32(5):1023-30. doi: 10.1007/s13277-011-0205-2. Epub 2011 Jul 1.
Several protein kinase C (PKC) isoforms have been shown to influence different cellular processes that may contribute to the malignancy of breast cancer cells. To obtain insight into mechanisms mediating the PKC effects, global gene expression was analyzed in MDA-MB-231 breast cancer cells in which PKCα, PKCδ or PKCε had been down-regulated with siRNA. Gene set enrichment analyses revealed that hypoxia-induced genes were enriched among genes that increased in PKCα-down-regulated cells. The STC1 mRNA, encoding stanniocalcin 1, was particularly up-regulated following depletion of PKCα and was also induced by hypoxia. Both hypoxia and PKCα down-regulation also led to increased STC1 protein levels. The results demonstrate that PKCα suppresses the expression of STC1 in breast cancer cells.
几种蛋白激酶C（PKC）亚型已被证明会影响不同的细胞过程，这些过程可能导致乳腺癌细胞的恶性化。为了深入了解介导PKC作用的机制，我们对MDA-MB-231乳腺癌细胞进行了全基因表达分析，其中PKCα、PKCδ或PKCε已通过siRNA下调。基因集富集分析显示，缺氧诱导基因在PKCα下调细胞中增加的基因中富集。编码鲽鱼钙蛋白1的STC1 mRNA在PKCα缺失后尤其上调，并且也由缺氧诱导。缺氧和PKCα下调均导致STC1蛋白水平升高。结果表明，PKCα抑制乳腺癌细胞中STC1的表达。
