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Published in: Tumor Biology 7/2016

01-07-2016 | Original Article

Evaluation of RIP1K and RIP3K expressions in the malignant and benign breast tumors

Authors: Fatemeh Karami-Tehrani, Amin Rahimi Malek, Zahra Shahsavari, Morteza Atri

Published in: Tumor Biology | Issue 7/2016

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Abstract

Receptor-interacting protein kinase 1 (RIP1K) and RIP3K belong to RIPK family, which regulate cell survival and cell death. In the present investigation, the expression levels of RIP1K and RIP3K were evaluated in the 30 malignant, 15 benign, and 20 normal breast tissues, and their correlation with clinicopathological characteristics was also studied. The expression levels of RIP1K and RIP3K were determined, by western blot analysis. The relative RIP1K expression was significantly higher in the malignant and benign tumors when compared to those of normal tissues (P < 0.0001 and P < 0.001, respectively). However, the expression level of RIP3K was significantly lower in the malignant tumors than those of normal and benign values (P < 0.001 and P < 0.01, respectively). Positive significant correlation was found for RIP1K expression with tumor size (P < 0.001), grades (P < 0.0001), and c-erbB2 (P < 0.001), but negative significant correlation was detected with patient’s age (P < 0.001), estrogen receptor (ER) (P < 0.001), progesterone receptor (PR) (P < 0.01), and P53 (P<0.01) status. RIP3K expression was significantly lower in the pre-menopauses (P < 0.01), grade III (P < 0.05), ER-negative (P < 0.05), and c-erbB2-negative malignant tumors, but no correlation was detected with tumor size, PR, and P53 status. No significant correlation was observed for RIP1K and RIP3K expressions with Ki67 and Her2. Based on the present results, it is concluded that reduction of RIP3K expression in the malignant breast tumor might be an important evidence to support the antitumor activity of this enzyme in vivo. However, RIP1K expression was shown to be higher in the malignant breast tumors than those of normal and benign breast tissues, which probably designates as a poor prognostic factor.
Literature
1.
go back to reference Ofengeim D, Y. J. Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death. Nat Rev Mol Cell Biol. 2013;14:727–36.CrossRefPubMed Ofengeim D, Y. J. Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death. Nat Rev Mol Cell Biol. 2013;14:727–36.CrossRefPubMed
4.
go back to reference Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009;137:1112–23.CrossRefPubMedPubMedCentral Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009;137:1112–23.CrossRefPubMedPubMedCentral
5.
go back to reference Sosna J, Voigt S, Mathieu S, Lange A, Thon L, Davarnia P, et al. TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death. Cell Mol Life Sci. 2014;71:331–48.CrossRefPubMed Sosna J, Voigt S, Mathieu S, Lange A, Thon L, Davarnia P, et al. TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death. Cell Mol Life Sci. 2014;71:331–48.CrossRefPubMed
6.
go back to reference Cho Y, McQuade T, Zhang H, Zhang J, Chan FK. RIP1-dependent and independent effects of necrostatin-1 in necrosis and t cell activation. PLoS One. 2011;6, e23209.CrossRefPubMedPubMedCentral Cho Y, McQuade T, Zhang H, Zhang J, Chan FK. RIP1-dependent and independent effects of necrostatin-1 in necrosis and t cell activation. PLoS One. 2011;6, e23209.CrossRefPubMedPubMedCentral
7.
go back to reference Green DR, Oberst A, Dillon CP, Weinlich R, Salvesen GS. RIPK-dependent necrosis and its regulation by caspases: a mystery in five acts. Mol Cell. 2011;44:9–16.CrossRefPubMedPubMedCentral Green DR, Oberst A, Dillon CP, Weinlich R, Salvesen GS. RIPK-dependent necrosis and its regulation by caspases: a mystery in five acts. Mol Cell. 2011;44:9–16.CrossRefPubMedPubMedCentral
8.
go back to reference Maki JL, Tres Brazell J, Teng X, Cuny GD, Degterev A. Expression and purification of active receptor interacting protein 1 kinase using a baculovirus system. Protein Expr Purif. 2013;89:156–61.CrossRefPubMedPubMedCentral Maki JL, Tres Brazell J, Teng X, Cuny GD, Degterev A. Expression and purification of active receptor interacting protein 1 kinase using a baculovirus system. Protein Expr Purif. 2013;89:156–61.CrossRefPubMedPubMedCentral
9.
go back to reference Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, et al. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell. 2008;30:689–700.CrossRefPubMed Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, et al. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell. 2008;30:689–700.CrossRefPubMed
10.
go back to reference Ramnarain DB, Paulmurugan R, Park S, Mickey BE, Asaithamby A, Saha D, et al. RIP1 links inflammatory and growth factor signaling pathways by regulating expression of the EGFR. Cell Death Differ. 2008;15:344–53.CrossRefPubMed Ramnarain DB, Paulmurugan R, Park S, Mickey BE, Asaithamby A, Saha D, et al. RIP1 links inflammatory and growth factor signaling pathways by regulating expression of the EGFR. Cell Death Differ. 2008;15:344–53.CrossRefPubMed
11.
go back to reference Moriwaki K, Bertin J, Gough PJ, Orlowski GM, Chan FK. Differential roles of RIPK1 and RIPK3 in TNF-induced necroptosis and chemotherapeutic agent-induced cell death. Cell Death Dis. 2015;6, e1636.CrossRefPubMedPubMedCentral Moriwaki K, Bertin J, Gough PJ, Orlowski GM, Chan FK. Differential roles of RIPK1 and RIPK3 in TNF-induced necroptosis and chemotherapeutic agent-induced cell death. Cell Death Dis. 2015;6, e1636.CrossRefPubMedPubMedCentral
12.
go back to reference O'Donnell MA, Perez-Jimenez E, Oberst A, Ng A, Massoumi R, Xavier R, et al. Caspase 8 inhibits programmed necrosis by processing cyld. Nat Cell Biol. 2011;13:1437–42.CrossRefPubMedPubMedCentral O'Donnell MA, Perez-Jimenez E, Oberst A, Ng A, Massoumi R, Xavier R, et al. Caspase 8 inhibits programmed necrosis by processing cyld. Nat Cell Biol. 2011;13:1437–42.CrossRefPubMedPubMedCentral
13.
go back to reference Feoktistova M, Leverkus M. Programmed necrosis and necroptosis signalling. FEBS J. 2015;282:19–31.CrossRefPubMed Feoktistova M, Leverkus M. Programmed necrosis and necroptosis signalling. FEBS J. 2015;282:19–31.CrossRefPubMed
14.
go back to reference Su X, Wang H, Kang D, Zhu J, Sun Q, Li T, et al. Necrostatin-1 ameliorates intracerebral hemorrhage-induced brain injury in mice through inhibiting RIP1/RIP3 pathway. Neurochem Res. 2015;40:643–50.CrossRefPubMed Su X, Wang H, Kang D, Zhu J, Sun Q, Li T, et al. Necrostatin-1 ameliorates intracerebral hemorrhage-induced brain injury in mice through inhibiting RIP1/RIP3 pathway. Neurochem Res. 2015;40:643–50.CrossRefPubMed
15.
go back to reference Vandenabeele P, Grootjans S, Callewaert N, Takahashi N. Necrostatin-1 blocks both RIPK1 and ido: consequences for the study of cell death in experimental disease models. Cell Death and Differentiation. 2013;20:185–7.CrossRefPubMed Vandenabeele P, Grootjans S, Callewaert N, Takahashi N. Necrostatin-1 blocks both RIPK1 and ido: consequences for the study of cell death in experimental disease models. Cell Death and Differentiation. 2013;20:185–7.CrossRefPubMed
16.
go back to reference Declercq W, Vanden Berghe T, Vandenabeele P. RIP kinases at the crossroads of cell death and survival. Cell. 2009;138:229–32.CrossRefPubMed Declercq W, Vanden Berghe T, Vandenabeele P. RIP kinases at the crossroads of cell death and survival. Cell. 2009;138:229–32.CrossRefPubMed
17.
go back to reference Salami S, Karami-Tehrani F. Biochemical studies of apoptosis induced by tamoxifen in estrogen receptor positive and negative breast cancer cell lines. Clin Biochem. 2003;36:247–53.CrossRefPubMed Salami S, Karami-Tehrani F. Biochemical studies of apoptosis induced by tamoxifen in estrogen receptor positive and negative breast cancer cell lines. Clin Biochem. 2003;36:247–53.CrossRefPubMed
18.
go back to reference Tavakoli-Yaraki M, Karami-Tehrani F, Salimi V, Sirati-Sabet M. Induction of apoptosis by trichostatin a in human breast cancer cell lines: Involvement of 15-LOX-1. Tumour Biol. 2013;34:241–9.CrossRefPubMed Tavakoli-Yaraki M, Karami-Tehrani F, Salimi V, Sirati-Sabet M. Induction of apoptosis by trichostatin a in human breast cancer cell lines: Involvement of 15-LOX-1. Tumour Biol. 2013;34:241–9.CrossRefPubMed
19.
go back to reference Aghaei M, Karami-Tehrani F, Salami S, Atri M. Adenosine deaminase activity in the serum and malignant tumors of breast cancer: the assessment of isoenzyme ADA1 and ADA2 activities. Clin Biochem. 2005;38:887–91.CrossRefPubMed Aghaei M, Karami-Tehrani F, Salami S, Atri M. Adenosine deaminase activity in the serum and malignant tumors of breast cancer: the assessment of isoenzyme ADA1 and ADA2 activities. Clin Biochem. 2005;38:887–91.CrossRefPubMed
20.
go back to reference Zhou W, Yuan J. Necroptosis in health and diseases. Seminars in cell and developmental biology. 2014;35:14–23.CrossRefPubMed Zhou W, Yuan J. Necroptosis in health and diseases. Seminars in cell and developmental biology. 2014;35:14–23.CrossRefPubMed
21.
go back to reference de Almagro MC, Vucic D. Necroptosis: pathway diversity and characteristics. Seminars in cell and developmental biology. 2015;39:56–62.CrossRefPubMed de Almagro MC, Vucic D. Necroptosis: pathway diversity and characteristics. Seminars in cell and developmental biology. 2015;39:56–62.CrossRefPubMed
22.
go back to reference Wang Q, Chen W, Xu X, Li B, He W, Padilla MT, et al. RIP1 potentiates BPDE-induced transformation in human bronchial epithelial cells through catalase-mediated suppression of excessive reactive oxygen species. Carcinogenesis. 2013;34:2119–28.CrossRefPubMedPubMedCentral Wang Q, Chen W, Xu X, Li B, He W, Padilla MT, et al. RIP1 potentiates BPDE-induced transformation in human bronchial epithelial cells through catalase-mediated suppression of excessive reactive oxygen species. Carcinogenesis. 2013;34:2119–28.CrossRefPubMedPubMedCentral
23.
go back to reference Wang Q, Chen W, Bai L, Chen W, Padilla MT, Lin AS, et al. Receptor-interacting protein 1 increases chemoresistance by maintaining inhibitor of apoptosis protein levels and reducing reactive oxygen species through a microRNA-146a-mediated catalase pathway. J Biol Chem. 2014;289:5654–63.CrossRefPubMedPubMedCentral Wang Q, Chen W, Bai L, Chen W, Padilla MT, Lin AS, et al. Receptor-interacting protein 1 increases chemoresistance by maintaining inhibitor of apoptosis protein levels and reducing reactive oxygen species through a microRNA-146a-mediated catalase pathway. J Biol Chem. 2014;289:5654–63.CrossRefPubMedPubMedCentral
24.
go back to reference Yu S, Hou D, Chen P, Zhang Q, Lv B, Ma Y, et al. Adenosine induces apoptosis through TNFR1/RIPK1/p38 axis in colon cancer cells. Biochem Biophys Res Commun. 2015;460:759–65.CrossRefPubMed Yu S, Hou D, Chen P, Zhang Q, Lv B, Ma Y, et al. Adenosine induces apoptosis through TNFR1/RIPK1/p38 axis in colon cancer cells. Biochem Biophys Res Commun. 2015;460:759–65.CrossRefPubMed
25.
go back to reference Liu XY, Lai F, Yan XG, Jiang CC, Guo ST, Wang CY, et al. RIP1 kinase is an oncogenic driver in melanoma. Cancer Res. 2015;75:1736–48.CrossRefPubMed Liu XY, Lai F, Yan XG, Jiang CC, Guo ST, Wang CY, et al. RIP1 kinase is an oncogenic driver in melanoma. Cancer Res. 2015;75:1736–48.CrossRefPubMed
26.
go back to reference Park S, Hatanpaa KJ, Xie Y, Mickey BE, Madden CJ, Raisanen JM, et al. The receptor interacting protein 1 inhibits p53 induction through nf-kappab activation and confers a worse prognosis in glioblastoma. Cancer Res. 2009;69:2809–16.CrossRefPubMedPubMedCentral Park S, Hatanpaa KJ, Xie Y, Mickey BE, Madden CJ, Raisanen JM, et al. The receptor interacting protein 1 inhibits p53 induction through nf-kappab activation and confers a worse prognosis in glioblastoma. Cancer Res. 2009;69:2809–16.CrossRefPubMedPubMedCentral
27.
go back to reference He S, Wang L, Miao L, Wang T, Du F, Zhao L, et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell. 2009;137:1100–11.CrossRefPubMed He S, Wang L, Miao L, Wang T, Du F, Zhao L, et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell. 2009;137:1100–11.CrossRefPubMed
28.
go back to reference Shahsavari Z, Karami-Tehrani F, Salami S, Ghasemzadeh M. RIP1K and RIP3K provoked by shikonin induces cell cycle arrest in the triple negative breast cancer cell line, MDA-MB-468: necroptosis as a desperate programmed suicide pathway. Tumor Biology. 2015. Shahsavari Z, Karami-Tehrani F, Salami S, Ghasemzadeh M. RIP1K and RIP3K provoked by shikonin induces cell cycle arrest in the triple negative breast cancer cell line, MDA-MB-468: necroptosis as a desperate programmed suicide pathway. Tumor Biology. 2015.
29.
go back to reference Koo GB, Morgan MJ, Lee DG, Kim WJ, Yoon JH, Koo JS, et al. Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics. Cell Res. 2015;25:707–25.CrossRefPubMedPubMedCentral Koo GB, Morgan MJ, Lee DG, Kim WJ, Yoon JH, Koo JS, et al. Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics. Cell Res. 2015;25:707–25.CrossRefPubMedPubMedCentral
30.
go back to reference Idirisinghe PK, Thike AA, Cheok PY, Tse GM, Lui PC, Fook-Chong S, et al. Hormone receptor and c-erbB2 status in distant metastatic and locally recurrent breast cancer. pathologic correlations and clinical significance. Am J Clin Pathol. 2010;133:416–29.CrossRefPubMed Idirisinghe PK, Thike AA, Cheok PY, Tse GM, Lui PC, Fook-Chong S, et al. Hormone receptor and c-erbB2 status in distant metastatic and locally recurrent breast cancer. pathologic correlations and clinical significance. Am J Clin Pathol. 2010;133:416–29.CrossRefPubMed
31.
go back to reference Lee A, Park WC, Yim HW, Lee MA, Park G, Lee KY. Expression of c-erbB2, cyclin D1 and estrogen receptor and their clinical implications in the invasive ductal carcinoma of the breast. Jpn J Clin Oncol. 2007;37:708–14.CrossRefPubMed Lee A, Park WC, Yim HW, Lee MA, Park G, Lee KY. Expression of c-erbB2, cyclin D1 and estrogen receptor and their clinical implications in the invasive ductal carcinoma of the breast. Jpn J Clin Oncol. 2007;37:708–14.CrossRefPubMed
32.
go back to reference Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M, et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat. 2013;139:539–52.CrossRefPubMedPubMedCentral Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M, et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat. 2013;139:539–52.CrossRefPubMedPubMedCentral
33.
go back to reference Panjehpour M, Karami-Tehrani F. An adenosine analog (IB-MECA) inhibits anchorage-dependent cell growth of various human breast cancer cell lines. Int J Biochem Cell Biol. 2004;36:1502–9.CrossRefPubMed Panjehpour M, Karami-Tehrani F. An adenosine analog (IB-MECA) inhibits anchorage-dependent cell growth of various human breast cancer cell lines. Int J Biochem Cell Biol. 2004;36:1502–9.CrossRefPubMed
34.
go back to reference Hashemi M, Karami-Tehrani F, Ghavami S, Maddika S, Los M. Adenosine and deoxyadenosine induces apoptosis in oestrogen receptor-positive and -negative human breast cancer cells via the intrinsic pathway. Cell Prolif. 2005;38:269–85.CrossRefPubMed Hashemi M, Karami-Tehrani F, Ghavami S, Maddika S, Los M. Adenosine and deoxyadenosine induces apoptosis in oestrogen receptor-positive and -negative human breast cancer cells via the intrinsic pathway. Cell Prolif. 2005;38:269–85.CrossRefPubMed
35.
go back to reference Panjehpour M, Karami-Tehrani F. Adenosine modulates cell growth in the human breast cancer cells via adenosine receptors. Oncol Res. 2007;16:575–85.CrossRefPubMed Panjehpour M, Karami-Tehrani F. Adenosine modulates cell growth in the human breast cancer cells via adenosine receptors. Oncol Res. 2007;16:575–85.CrossRefPubMed
36.
go back to reference Aghaei M, Panjehpour M, Karami-Tehrani F, Salami S. Molecular mechanisms of A3 adenosine receptor-induced G1 cell cycle arrest and apoptosis in androgen-dependent and independent prostate cancer cell lines: Involvement of intrinsic pathway. J Cancer Res Clin Oncol. 2011;137:1511–23.CrossRefPubMed Aghaei M, Panjehpour M, Karami-Tehrani F, Salami S. Molecular mechanisms of A3 adenosine receptor-induced G1 cell cycle arrest and apoptosis in androgen-dependent and independent prostate cancer cell lines: Involvement of intrinsic pathway. J Cancer Res Clin Oncol. 2011;137:1511–23.CrossRefPubMed
Metadata
Title
Evaluation of RIP1K and RIP3K expressions in the malignant and benign breast tumors
Authors
Fatemeh Karami-Tehrani
Amin Rahimi Malek
Zahra Shahsavari
Morteza Atri
Publication date
01-07-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 7/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4762-7

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