Early synergistic interactions between the HPV16‑E7 oncoprotein and 17β-oestradiol for repressing the expression of Granzyme B in a cervical cancer model

Munguía-Moreno,J.   Antonio; Díaz‑Chavéz,José; García-Villa,Enrique; Albino-Sanchez,M.   Estela; Mendoza-Villanueva,Daniel; Ocadiz-Delgado,Rodolfo; Bonilla-Delgado,José; Marín‑Flores,Armando; Cortés-Malagón,Enoc   M.; Alvarez-Rios,Elizabeth; Hidalgo-Miranda,Alfredo; Üren,Aykut; Çelik,Haydar; Lambert,Paul  F.; Gariglio,Patricio

doi:10.3892/ijo.2018.4432

Early synergistic interactions between the HPV16‑E7 oncoprotein and 17β-oestradiol for repressing the expression of Granzyme B in a cervical cancer model

Authors:
- J. Antonio Munguía-Moreno
- José Díaz‑Chavéz
- Enrique García-Villa
- M. Estela Albino-Sanchez
- Daniel Mendoza-Villanueva
- Rodolfo Ocadiz-Delgado
- José Bonilla-Delgado
- Armando Marín‑Flores
- Enoc M. Cortés-Malagón
- Elizabeth Alvarez-Rios
- Alfredo Hidalgo-Miranda
- Aykut Üren
- Haydar Çelik
- Paul F. Lambert
- Patricio Gariglio
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Affiliations: Department of Genetics and Molecular Biology, Centre for Research and Advanced Studies of the National Polytechnic Institute, México City 07360, México, Biomedical Unit for Cancer Research, National Autonomous University of Mexico/National Institute of Cancer, México City 14080, México, Laboratory of Cell and Developmental Signalling, National Cancer Institute at Frederick, Frederick, MD 21702, USA, Research Unit of Genetics and Cancer, Juárez Hospital, México City 07760, México, Department of Oncogenomics, National Institute of Genomic Medicine, México City 14610, México, México, Department of Oncology, Lombardi Comprehensive Cancer Centre, Georgetown University Medical Centre, Washington, DC 20057, USA, McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
Published online on: June 6, 2018 https://doi.org/10.3892/ijo.2018.4432
Pages: 579-591
Copyright: © Munguía-Moreno et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although high-risk human papillomavirus (HR‑HPV) infection has a prominent role in the aetiology of cervical cancer (CC), sex steroid hormones may also be involved in this process; however, the cooperation between oestrogen and HR‑HPV in the early stages of cervical carcinogenesis is poorly understood. Since 17β-oestradiol (E2) and the HPV type 16‑E7 oncoprotein induce CC in transgenic mice, a microarray analysis was performed in the present study to generate global gene expression profiles from 2‑month‑old FVB (non‑transgenic) and K14E7 (transgenic) mice who were left untreated or were treated for 1 month with E2. Upregulation of cancer-related genes that have not been previously reported in the context of CC, including glycerophosphodiester phosphodiesterase domain containing 3, interleukin 1 receptor type II, natriuretic peptide type C, MGAT4 family member C, lecithin-retinol acyltransferase (phosphatidylcholine-retinol-O-acyltransferase) and glucoside xylosyltransferase 2, was observed. Notably, upregulation of the serine (or cysteine) peptidase inhibitor clade B member 9 gene and downregulation of the Granzyme gene family were observed; the repression of the Granzyme B pathway may be a novel mechanism of immune evasion by cancer cells. The present results provide the basis for further studies on early biomarkers of CC risk and synergistic interactions between HR‑HPV and oestrogen.

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1	zur Hausen H: Papillomaviruses in the causation of human cancers - a brief historical account. Virology. 384:260–265. 2009. View Article : Google Scholar
2	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar
3	Smith JS, Lindsay L, Hoots B, Keys J, Franceschi S, Winer R and Clifford GM: Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update. Int J Cancer. 121:621–632. 2007. View Article : Google Scholar
4	Riley RR, Duensing S, Brake T, Münger K, Lambert PF and Arbeit JM: Dissection of human papillomavirus E6 and E7 function in transgenic mouse models of cervical carcinogenesis. Cancer Res. 63:4862–4871. 2003.
5	Brake T and Lambert PF: Estrogen contributes to the onset, persistence, and malignant progression of cervical cancer in a human papillomavirus-transgenic mouse model. Proc Natl Acad Sci USA. 102:2490–2495. 2005. View Article : Google Scholar
6	Chung SH, Wiedmeyer K, Shai A, Korach KS and Lambert PF: Requirement for estrogen receptor alpha in a mouse model for human papillomavirus-associated cervical cancer. Cancer Res. 68:9928–9934. 2008. View Article : Google Scholar
7	Cortés-Malagón EM, Bonilla-Delgado J, Díaz-Chávez J, Hidalgo-Miranda A, Romero-Cordoba S, Uren A, Celik H, McCormick M, Munguía-Moreno JA, Ibarra-Sierra E, et al: Gene expression profile regulated by the HPV16 E7 oncoprotein and estradiol in cervical tissue. Virology. 447:155–165. 2013. View Article : Google Scholar
8	Nickens KP, Han Y, Shandilya H, Larrimore A, Gerard GF, Kaldjian E, Patierno SR and Ceryak S: Acquisition of mitochondrial dysregulation and resistance to mitochondrial-mediated apoptosis after genotoxic insult in normal human fibroblasts: A possible model for early stage carcinogenesis. Biochim Biophys Acta. 1823:264–272. 2012. View Article : Google Scholar
9	Rousalova I and Krepela E: Granzyme B-induced apoptosis in cancer cells and its regulation (review). Int J Oncol. 37:1361–1378. 2010.
10	Berthou C, Michel L, Soulié A, Jean-Louis F, Flageul B, Dubertret L, Sigaux F, Zhang Y and Sasportes M: Acquisition of granzyme B and Fas ligand proteins by human keratinocytes contributes to epidermal cell defense. J Immunol. 159:5293–5300. 1997.
11	Hernandez-Pigeon H, Jean C, Charruyer A, Haure MJ, Titeux M, Tonasso L, Quillet-Mary A, Baudouin C, Charveron M and Laurent G: Human keratinocytes acquire cellular cytotoxicity under UV-B irradiation. Implication of granzyme B and perforin J Biol Chem. 281:13525–13532. 2006.
12	Fang Y, Herrick EJ and Nicholl MB: A possible role for perforin and granzyme B in resveratrol-enhanced radiosensitivity of prostate cancer. J Androl. 33:752–760. 2012. View Article : Google Scholar
13	Hernandez-Pigeon H, Jean C, Charruyer A, Haure MJ, Baudouin C, Charveron M, Quillet-Mary A and Laurent G: UVA induces granzyme B in human keratinocytes through MIF: Implication in extracellular matrix remodeling. J Biol Chem. 282:8157–8164. 2007. View Article : Google Scholar
14	Boivin WA, Cooper DM, Hiebert PR and Granville DJ: Intracellular versus extracellular granzyme B in immunity and disease: Challenging the dogma. Lab Invest. 89:1195–1220. 2009. View Article : Google Scholar
15	Khan MS, Singh P, Azhar A, Naseem A, Rashid Q, Kabir MA and Jairajpuri MA: Serpin inhibition mechanism: A delicate balance between native metastable state and polymerization. J Amino Acids. 2011:6067972011. View Article : Google Scholar
16	Medema JP, de Jong J, Peltenburg LT, Verdegaal EM, Gorter A, Bres SA, Franken KL, Hahne M, Albar JP, Melief CJ, et al: Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proc Natl Acad Sci USA. 98:11515–11520. 2001. View Article : Google Scholar
17	Herber R, Liem A, Pitot H and Lambert PF: Squamous epithelial hyperplasia and carcinoma in mice transgenic for the human papillomavirus type 16 E7 oncogene. J Virol. 70:1873–1881. 1996.
18	Ibarra Sierra E, Díaz Chávez J, Cortés-Malagón EM, Uribe-Figueroa L, Hidalgo-Miranda A, Lambert PF and Gariglio P: Differential gene expression between skin and cervix induced by the E7 oncoprotein in a transgenic mouse model. Virology. 433:337–345. 2012. View Article : Google Scholar
19	Kendziorski C, Irizarry RA, Chen KS, Haag JD and Gould MN: On the utility of pooling biological samples in microarray experiments. Proc Natl Acad Sci USA. 102:4252–4257. 2005. View Article : Google Scholar
20	Chabas D, Baranzini SE, Mitchell D, Bernard CC, Rittling SR, Denhardt DT, Sobel RA, Lock C, Karpuj M, Pedotti R, et al: The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease. Science. 294:1731–1735. 2001. View Article : Google Scholar
21	Kainkaryam RM, Bruex A, Gilbert AC, Schiefelbein J and Woolf PJ: poolMC: Smart pooling of mRNA samples in microarray experiments. BMC Bioinformatics. 11:2992010. View Article : Google Scholar
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar
23	McLaughlin-Drubin ME, Crum CP and Münger K: Human papillomavirus E7 oncoprotein induces KDM6A and KDM6B histone demethylase expression and causes epigenetic reprogramming. Proc Natl Acad Sci USA. 108:2130–2135. 2011. View Article : Google Scholar
24	McLaughlin-Drubin ME, Park D and Munger K: Tumor suppressor p16^INK4A is necessary for survival of cervical carcinoma cell lines. Proc Natl Acad Sci USA. 110:16175–16180. 2013. View Article : Google Scholar
25	Yim EK and Park JS: Biomarkers in cervical cancer. Biomark Insights. 1:215–225. 2007.
26	Chung SH, Franceschi S and Lambert PF: Estrogen and ERalpha: Culprits in cervical cancer. Trends Endocrinol Metab. 21:504–511. 2010. View Article : Google Scholar
27	den Boon JA, Pyeon D, Wang SS, Horswill M, Schiffman M, Sherman M, Zuna RE, Wang Z, Hewitt SM, Pearson R, et al: Molecular transitions from papillomavirus infection to cervical precancer and cancer: Role of stromal estrogen receptor signaling. Proc Natl Acad Sci USA. 112:E3255–E3264. 2015. View Article : Google Scholar
28	Dozmorov MG, Giles CB and Wren JD: Predicting gene ontology from a global meta-analysis of 1-color microarray experiments. BMC Bioinformatics. 12(Suppl 10): S142011. View Article : Google Scholar
29	Cairns RA, Harris IS and Mak TW: Regulation of cancer cell metabolism. Nat Rev Cancer. 11:85–95. 2011. View Article : Google Scholar
30	Zhang F and Du G: Dysregulated lipid metabolism in cancer. World J Biol Chem. 3:167–174. 2012. View Article : Google Scholar
31	Menendez JA and Lupu R: Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer. 7:763–777. 2007. View Article : Google Scholar
32	Röhrig F and Schulze A: The multifaceted roles of fatty acid synthesis in cancer. Nat Rev Cancer. 16:732–749. 2016. View Article : Google Scholar
33	Baenke F, Peck B, Miess H and Schulze A: Hooked on fat: The role of lipid synthesis in cancer metabolism and tumour development. Dis Model Mech. 6:1353–1363. 2013. View Article : Google Scholar
34	Henderson BE, Ross RK, Pike MC and Casagrande JT: Endogenous hormones as a major factor in human cancer. Cancer Res. 42:3232–3239. 1982.
35	Furth J: A meeting of ways in cancer research: Thoughts on the evolution and nature of neoplasms. Cancer Res. 19:241–258. 1959.
36	Arbeit JM, Howley PM and Hanahan D: Chronic estrogen-induced cervical and vaginal squamous carcinogenesis in human papillomavirus type 16 transgenic mice. Proc Natl Acad Sci USA. 93:2930–2935. 1996. View Article : Google Scholar
37	Nielsen SJ, Gøtze JP, Jensen HL and Rehfeld JF: ProCNP and CNP are expressed primarily in male genital organs. Regul Pept. 146:204–212. 2008. View Article : Google Scholar
38	Nielsen SJ, Iversen P, Rehfeld JF, Jensen HL and Goetze JP: C-type natriuretic peptide in prostate cancer. APMIS. 117:60–67. 2009. View Article : Google Scholar
39	Scotland RS, Ahluwalia A and Hobbs AJ: C-type natriuretic peptide in vascular physiology and disease. Pharmacol Ther. 105:85–93. 2005. View Article : Google Scholar
40	Grinde MT, Skrbo N, Moestue SA, Rødland EA, Borgan E, Kristian A, Sitter B, Bathen TF, Børresen-Dale AL, Mælandsmo GM, et al: Interplay of choline metabolites and genes in patient-derived breast cancer xenografts. Breast Cancer Res. 16:R52014. View Article : Google Scholar
41	Demichelis F, Setlur SR, Banerjee S, Chakravarty D, Chen JY, Chen CX, Huang J, Beltran H, Oldridge DA, Kitabayashi N, et al: Identification of functionally active, low frequency copy number variants at 15q21.3 and 12q21.31 associated with prostate cancer risk. Proc Natl Acad Sci USA. 109:6686–6691. 2012. View Article : Google Scholar
42	Mar AC, Chu CH, Lee HJ, Chien CW, Cheng JJ, Yang SH, Jiang JK and Lee TC: Interleukin-1 receptor type 2 acts with c-Fos to enhance the expression of interleukin-6 and vascular endothelial growth factor A in colon cancer cells and induce angiogenesis. J Biol Chem. 290:22212–22224. 2015. View Article : Google Scholar
43	Amann PM, Czaja K, Bazhin AV, Rühl R, Eichmüller SB, Merk HF and Baron JM: LRAT overexpression diminishes intracellular levels of biologically active retinoids and reduces retinoid antitumor efficacy in the murine melanoma B16F10 cell line. Skin Pharmacol Physiol. 28:205–212. 2015. View Article : Google Scholar
44	Hiebert PR and Granville DJ: Granzyme B in injury, inflammation, and repair. Trends Mol Med. 18:732–741. 2012. View Article : Google Scholar
45	Provenzano PP, Inman DR, Eliceiri KW, Knittel JG, Yan L, Rueden CT, White JG and Keely PJ: Collagen density promotes mammary tumor initiation and progression. BMC Med. 6:112008. View Article : Google Scholar
46	Saito S, Murakoshi K, Kotake S, Kamatani N and Tomatsu T: Granzyme B induces apoptosis of chondrocytes with natural killer cell-like cytotoxicity in rheumatoid arthritis. J Rheumatol. 35:1932–1943. 2008.
47	Parkinson LG, Toro A, Zhao H, Brown K, Tebbutt SJ and Granville DJ: Granzyme B mediates both direct and indirect cleavage of extracellular matrix in skin after chronic low-dose ultraviolet light irradiation. Aging Cell. 14:67–77. 2015. View Article : Google Scholar
48	Meyaard L: The inhibitory collagen receptor LAIR-1 (CD305). J Leukoc Biol. 83:799–803. 2008. View Article : Google Scholar
49	Vesely MD, Kershaw MH, Schreiber RD and Smyth MJ: Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 29:235–271. 2011. View Article : Google Scholar
50	Salmon H, Franciszkiewicz K, Damotte D, Dieu-Nosjean MC, Validire P, Trautmann A, Mami-Chouaib F and Donnadieu E: Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J Clin Invest. 122:899–910. 2012. View Article : Google Scholar
51	Sorokin L: The impact of the extracellular matrix on inflammation. Nat Rev Immunol. 10:712–723. 2010. View Article : Google Scholar
52	Weathington NM, van Houwelingen AH, Noerager BD, Jackson PL, Kraneveld AD, Galin FS, Folkerts G, Nijkamp FP and Blalock JE: A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation. Nat Med. 12:317–323. 2006. View Article : Google Scholar
53	Jadhav RR, Ye Z, Huang RL, Liu J, Hsu PY, Huang YW, Rangel LB, Lai HC, Roa JC, Kirma NB, et al: Genome-wide DNA methylation analysis reveals estrogen-mediated epigenetic repression of metallothionein-1 gene cluster in breast cancer. Clin Epigenetics. 7:132015. View Article : Google Scholar
54	Laurson J, Khan S, Chung R, Cross K and Raj K: Epigenetic repression of E-cadherin by human papillomavirus 16 E7 protein. Carcinogenesis. 31:918–926. 2010. View Article : Google Scholar
55	McLane LM, Banerjee PP, Cosma GL, Makedonas G, Wherry EJ, Orange JS and Betts MR: Differential localization of T-bet and Eomes in CD8 T cell memory populations. J Immunol. 190:3207–3215. 2013. View Article : Google Scholar
56	Fukuoka N, Harada M, Nishida A, Ito Y, Shiota H and Kataoka T: Eomesodermin promotes interferon-γ expression and binds to multiple conserved noncoding sequences across the Ifng locus in mouse thymoma cell lines. Genes Cells. 21:146–162. 2016. View Article : Google Scholar
57	Banno T, Adachi M, Mukkamala L and Blumenberg M: Unique keratinocyte-specific effects of interferon-gamma that protect skin from viruses, identified using transcriptional profiling. Antivir Ther. 8:541–554. 2003.
58	Black AP, Ardern-Jones MR, Kasprowicz V, Bowness P, Jones L, Bailey AS and Ogg GS: Human keratinocyte induction of rapid effector function in antigen-specific memory CD4⁺ and CD8⁺ T cells. Eur J Immunol. 37:1485–1493. 2007. View Article : Google Scholar
59	Soriano C, Mukaro V, Hodge G, Ahern J, Holmes M, Jersmann H, Moffat D, Meredith D, Jurisevic C, Reynolds PN, et al: Increased proteinase inhibitor-9 (PI-9) and reduced granzyme B in lung cancer: Mechanism for immune evasion. Lung Cancer. 77:38–45. 2012. View Article : Google Scholar
60	Bird CH, Sutton VR, Sun J, Hirst CE, Novak A, Kumar S, Trapani JA, Bird PI, et al: Selective regulation of apoptosis: The cytotoxic lymphocyte serpin proteinase inhibitor 9 protects against granzyme B-mediated apoptosis without perturbing the Fas cell death pathway. Mol Cell Biol. 18:6387–6398. 1998. View Article : Google Scholar
61	Buzza MS, Hirst CE, Bird CH, Hosking P, McKendrick J and Bird PI: The granzyme B inhibitor, PI-9, is present in endothelial and mesothelial cells, suggesting that it protects bystander cells during immune responses. Cell Immunol. 210:21–29. 2001. View Article : Google Scholar
62	Barrie MB, Stout HW, Abougergi MS, Miller BC and Thiele DL: Antiviral cytokines induce hepatic expression of the granzyme B inhibitors, proteinase inhibitor 9 and serine proteinase inhibitor 6. J Immunol. 172:6453–6459. 2004. View Article : Google Scholar
63	Jiang X, Orr BA, Kranz DM and Shapiro DJ: Estrogen induction of the granzyme B inhibitor, proteinase inhibitor 9, protects cells against apoptosis mediated by cytotoxic T lymphocytes and natural killer cells. Endocrinology. 147:1419–1426. 2006. View Article : Google Scholar
64	Lauricella M, Carlisi D, Giuliano M, Calvaruso G, Cernigliaro C, Vento R and D'Anneo A: The analysis of estrogen receptor-α positive breast cancer stem-like cells unveils a high expression of the serpin proteinase inhibitor PI-9: Possible regulatory mechanisms. Int J Oncol. 49:352–360. 2016. View Article : Google Scholar
65	Cunningham TD, Jiang X and Shapiro DJ: Expression of high levels of human proteinase inhibitor 9 blocks both perforin/granzyme and Fas/Fas ligand-mediated cytotoxicity. Cell Immunol. 245:32–41. 2007. View Article : Google Scholar
66	Deisting W, Raum T, Kufer P, Baeuerle PA and Münz M: Impact of diverse immune evasion mechanisms of cancer cells on T cells engaged by EpCAM/CD3-bispecific antibody construct AMG 110. PLoS One. 10:e01416692015. View Article : Google Scholar
67	Bladergroen BA, Meijer CJ, ten Berge RL, Hack CE, Muris JJ, Dukers DF, Chott A, Kazama Y, Oudejans JJ, van Berkum O, et al: Expression of the granzyme B inhibitor, protease inhibitor 9, by tumor cells in patients with non-Hodgkin and Hodgkin lymphoma: A novel protective mechanism for tumor cells to circumvent the immune system. Blood. 99:232–237. 2002. View Article : Google Scholar
68	Fritsch K, Finke J and Grüllich C: Suppression of granzyme B activity and caspase-3 activation in leukaemia cells constitutively expressing the protease inhibitor 9. Ann Hematol. 92:1603–1609. 2013. View Article : Google Scholar