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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2009

01-03-2009 | Preclinical Study

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

Authors: René Nieves-Alicea, Nancy H. Colburn, Ann-Marie Simeone, Ana M. Tari

Published in: Breast Cancer Research and Treatment | Issue 2/2009

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Abstract

High levels of the cyclooxygenase-2 (COX-2) protein have been associated with invasion and metastasis of breast tumors. Both prostaglandin E2 (PGE2) 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 PGE2 and IL-8 to induce breast cancer cell invasion. We demonstrated that PGE2 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 PGE2 and IL-8. In MCF-7 cells overexpressing PDCD4 (MCF-7/PDCD4), PGE2 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 PGE2 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 PGE2 and IL-8, and that PDCD4 increases TIMP-2 expression to inhibit breast cancer cell invasion.
Literature
1.
Ries L, Melbert D, Krapcho M et al (2007) SEER Cancer Statistic Review, 1975–2004, National Cancer Institute. Bethesda, MD. Available via INTERNET http://​seer.​cancer.​gov/​csr/​1975_​2004/​, based on November 2006 SEER data submission, posted to the SEER web site, 2007. Cited 2 Feb 2007
2.
Denkert C, Winzer KJ, Muller BM et al (2003) Elevated expression of cyclooxygenase-2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma. Cancer 97(12):2978–2987PubMedCrossRef
3.
Ristimaki A, Sivula A, Lundin J et al (2002) Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res 62(3):632–635PubMed
4.
Soslow RA, Dannenberg AJ, Rush D et al (2000) COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 89(12):2637–2645PubMedCrossRef
5.
Larkins TL, Nowell M, Singh S et al (2006) Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression. BMC Cancer 6:181–193PubMedCrossRef
6.
Simeone AM, Nieves-Alicea R, McMurtry VC et al (2007) Cyclooxygenase-2 uses the protein kinase C/interleukin-8/urokinase-type plasminogen activator pathway to increase the invasiveness of breast cancer cells. Int J Oncol 30(4):785–792PubMed
7.
Singh B, Berry JA, Shoher A et al (2005) COX-2 overexpression increases motility and invasion of breast cancer cells. Int J Oncol 26(5):1393–1399PubMed
8.
Zhang Z, DuBois RN (2001) Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor. Oncogene 20(33):4450–4456PubMedCrossRef
9.
Yang HS, Jansen AP, Nair R et al (2001) A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-kappaB or ODC transactivation. Oncogene 20(6):669–676PubMedCrossRef
10.
Cmarik JL, Min H, Hegamyer G et al (1999) Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation. Proc Natl Acad Sci USA 96(24):14037–14042PubMedCrossRef
11.
Jansen AP, Camalier CE, Colburn NH (2005) Epidermal expression of the translation inhibitor programmed cell death 4 suppresses tumorigenesis. Cancer Res 65(14):6034–6041PubMedCrossRef
12.
Yang HS, Jansen AP, Komar AA et al (2003) The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation. Mol Cell Biol 23(1):26–37PubMedCrossRef
13.
Goke R, Barth P, Schmidt A et al (2004) Programmed cell death protein 4 suppresses CDK1/cdc2 via induction of p21(Waf1/Cip1). Am J Physiol Cell Physiol 287(6):C1541–C1546PubMedCrossRef
14.
Jansen AP, Camalier CE, Stark C et al (2004) Characterization of programmed cell death 4 in multiple human cancers reveals a novel enhancer of drug sensitivity. Mol Cancer Ther 3(2):103–110PubMed
15.
Chen Y, Knosel T, Kristiansen G et al (2003) Loss of PDCD4 expression in human lung cancer correlates with tumour progression and prognosis. J Pathol 200(5):640–646PubMedCrossRef
16.
Ma G, Guo KJ, Zhang H et al (2005) Expression of programmed cell death 4 and its clinicopathological significance in human pancreatic cancer. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 27(5):597–600PubMed
17.
Zhang H, Ozaki I, Mizuta T et al (2006) Involvement of programmed cell death 4 in transforming growth factor-beta1-induced apoptosis in human hepatocellular carcinoma. Oncogene 25(45):6101–6112PubMedCrossRef
18.
Mudduluru G, Medved F, Grobholz R et al (2007) Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer. Cancer 110(8):1697–1707PubMedCrossRef
19.
Gao F, Zhang P, Zhou C et al (2007) Frequent loss of PDCD4 expression in human glioma: possible role in the tumorigenesis of glioma. Oncol Rep 17(1):123–128PubMed
20.
Wen YH, Shi X, Chiriboga L et al (2007) Alterations in the expression of PDCD4 in ductal carcinoma of the breast. Oncol Rep 18(6):1387–1393PubMed
21.
Leupold JH, Yang HS, Colburn NH et al (2007) Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors. Oncogene 26(31):4550–4562PubMedCrossRef
22.
Yang HS, Matthews CP, Clair T et al (2006) Tumorigenesis suppressor Pdcd4 down-regulates mitogen-activated protein kinase kinase kinase kinase 1 expression to suppress colon carcinoma cell invasion. Mol Cell Biol 26(4):1297–1306PubMedCrossRef
23.
Wang Q, Sun Z, Yang HS (2008) Downregulation of tumor suppressor Pdcd4 promotes invasion and activates both beta-catenin/Tcf and AP-1-dependent transcription in colon carcinoma cells. Oncogene 27(11):1527–1535PubMedCrossRef
24.
Tari AM, Simeone AM, Li YJ et al (2005) Cyclooxygenase-2 protein reduces tamoxifen and N-(4-hydroxyphenyl)retinamide inhibitory effects in breast cancer cells. Lab Invest 85(11):1357–1367PubMedCrossRef
25.
Ahn SM, Jeong SJ, Kim YS et al (2004) Retroviral delivery of TIMP-2 inhibits H-ras-induced migration and invasion in MCF10A human breast epithelial cells. Cancer Lett 207(1):49–57PubMedCrossRef
26.
Yoneda T, Sasaki A, Dunstan C et al (1997) Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2. J Clin Invest 99(10):2509–2517PubMedCrossRef
27.
Sacco MG, Cato EM, Ceruti R et al (2001) Systemic gene therapy with anti-angiogenic factors inhibits spontaneous breast tumor growth and metastasis in MMTVneu transgenic mice. Gene Ther 8(1):67–70PubMedCrossRef
28.
Ree AH, Florenes VA, Berg JP et al (1997) High levels of messenger RNAs for tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in primary breast carcinomas are associated with development of distant metastases. Clin Cancer Res 3(9):1623–1628PubMed
29.
Vizoso FJ, Gonzalez LO, Corte MD et al (2007) Study of matrix metalloproteinases and their inhibitors in breast cancer. Br J Cancer 96(6):903–911PubMedCrossRef
30.
Jiang Y, Goldberg ID, Shi YE (2002) Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene 21(14):2245–2252PubMedCrossRef
31.
Dorrello NV, Peschiaroli A, Guardavaccaro D et al (2006) S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science 314(5798):467–471PubMedCrossRef
32.
Ozpolat B, Akar U, Steiner M et al (2007) Programmed cell death-4 tumor suppressor protein contributes to retinoic acid-induced terminal granulocytic differentiation of human myeloid leukemia cells. Mol Cancer Res 5(1):95–108PubMedCrossRef
33.
Frankel LB, Christoffersen NR, Jacobsen A et al (2008) Programmed Cell Death 4 (PDCD4) is an important functional target of the MicroRNA miR-21 in breast cancer cells. J Biol Chem 283(2):1026–1033PubMedCrossRef
34.
Asangani IA, Rasheed SA, Nikolova DA, et al (2007) MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. Advance online publication October 29
Metadata
Title
Programmed Cell Death 4 inhibits breast cancer cell invasion by increasing Tissue Inhibitor of Metalloproteinases-2 expression
Authors
René Nieves-Alicea
Nancy H. Colburn
Ann-Marie Simeone
Ana M. Tari
Publication date
01-03-2009
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-008-9993-5

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