Programmed Cell Death 4 inhibits breast cancer cell invasion by increasing Tissue Inhibitor of Metalloproteinases-2 expression

来自 EBSCO

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作者：

R Nieves-Alicea，NH Colburn，AM Simeone，AM Tari

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摘要：

High levels of the cyclooxygenase-2 ( COX-2 ) protein have been associated with invasion and metastasis of breast tumors. Both prostaglandin E 2 (PGE 2 ) and interleukin-8 (IL-8) have been shown to mediate the invasive activity of COX-2 in breast cancer cells. Here we expand these studies to determine how COX-2 uses PGE 2 and IL-8 to induce breast cancer cell invasion. We demonstrated that PGE 2 and IL-8 decreased the expression of the tumor suppressor protein Programmed Cell Death 4 (PDCD4). We hypothesized that suppression of PDCD4 expression is vital to the invasive activity of PGE 2 and IL-8. In MCF-7 cells overexpressing PDCD4 (MCF-7/PDCD4), PGE 2 and IL-8 failed to induce invasion, in contrast to the parental MCF-7 cells, thus indicating that PDCD4 blocks breast cancer cell invasion. MCF-7/PDCD4 cells produced higher levels of the Tissue Inhibitor of Metalloproteinases-2 ( TIMP-2 ) than the parental cells. Silencing TIMP-2 mRNA in MCF-7/PDCD4 cells reversed the anti-invasive effects of PDCD4, allowing PGE 2 and IL-8 to induce the invasion of these cells. Here we report the novel findings that suppression of PDCD4 expression is vital for the invasive activity of COX-2 mediated by PGE 2 and IL-8, and that PDCD4 increases TIMP-2 expression to inhibit breast cancer cell invasion.

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关键词：

Breast cancer invasion Interleukin-8 Programmed Cell Death 4 Prostaglandin E2 Tissue Inhibitor of Metalloproteinase-2

DOI：

10.1007/s10549-008-9993-5

被引量：

158

年份：

2009