Abstract
Previous study has demonstrated that squamous cell carcinoma antigen (SCCA) 1 attenuates apoptosis induced by TNFα, NK cell or anticancer drug. In this study, we have examined the effect of SCCA2, which is highly homologous to SCCA1, but has different target specificity, against radiation-induced apoptosis, together with that of SCCA1. We demonstrated that cell death induced by radiation treatment was remarkably suppressed not only in SCCA1 cDNA-transfected cells, but also in SCCA2 cDNA-transfected cells. In these transfectants, caspase 3 activity and the expression of activated caspase 9 after radiation treatment were suppressed. Furthermore, the expression level of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) was suppressed compared to that of the control cells. The expression level of upstream stimulator of p38 MAPK, phosphorylated MKK3/MKK6, was also suppressed in the radiation-treated cells. Thus, both SCCA1 and SCCA2 may contribute to survival of the squamous cells from radiation-induced apoptosis by regulating p38 MAPK pathway. © 2001 Cancer Research Campaign
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Alnemri ES, Livingston DJ, Nicholson DW, Selveson G, Thornberry NA, Wong WW and Yuan J (1996) Human ICE/CED-3 protease nomenclature [letter]. Cell 87: 171
Belin D, Wohlwend A, Schleuning WD, Kruithof EK and Vassalli JD (1989) Facultative polypeptide translocation allows a single mRNA to encode the secreted and cytosolic forms of plasminogen activators inhibitor 2. EMBO J 8: 3287–3294
Bird PI (1999) Regulation of pro-apoptotic leucocyte granule serine proteinases by intracellular serpins. Immunol Cell Biol 77: 47–57
Bird CH, Sutton VR, Sun J, Hirst CE, Novak A, Kumar S, Trapani JA and Bird PI (1998) 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
Brenner B, Koppenhoefer U, Weinstock C, Linderkamp O, Lang F and Gulbins E (1997) Fas- or ceramide-induced apoptosis is mediated by a Rac1-regulated activation of Jun N-terminal kinase/p38 kinases and GADD153. J Biol Chem 272: 22173–22181
Brioschi PA, Bischof P, Delafosse C and Krauer F (1991) Squamous-cell carcinoma antigen (SCC-A) values related to clinical outcome of pre-invasive and invasive cervical carcinoma. Int J Cancer 47: 376–379
Chen YR, Meyer CF and Tan TH (1996a) Persistent activation of c-Jun N-terminal kinase 1 (JNK1) in γ radiation-induced apoptosis. J Biol Chem 271: 631–634
Chen YR, Wang X, Templeton D, Davis RJ and Tan TH (1996b) The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and γ radiation. J Biol Chem 271: 31929–31936
Chen Z, Seimiya H, Naito M, Mashima T, Kizaki A, Dan S, Imaizumi M, Ichijo H, Miyazono K and Tsuruo T (1999) ASK mediates apoptotic cell death induced by genotoxic stress. Oncogene 18: 173–180
Cobb MH and Goldsmith EJ (1995) How MAP kinase are regulated. J Biol Chem 270: 14843–14846
Cohen GM (1997) Caspases: the executioners of apoptosis. Biochem J 326: 1–16
Dickens M, Rogers JS, Cavanagh J, Raitano A, Xia Z, Halpern JR, Greenberg ME, Sawyers CL and Davis RJ (1997) A cytoplasmic inhibitor of the JNK signal transduction pathway. Science 277: 693–696
Enari M, Hug H and Nagata S (1995) Involvement of an ICE-like protease in Fas-mediated apoptosis. Nature 375: 78–81
Furuya Y, Krajewski S, Epstein JI and Issacs JT (1996) Expression of bcl-2 and the progression of human and rodent prostatic cancers. Clin Cancer Res 2: 389–398
Guo YL, Baysal K, Kang B, Yang LJ and Williamson JR (1998) Correlation between sustained c-Jun N-terminal protein kinase activation and apoptosis induced by tumour necrosis factor-α in rat mesangial cells. J Biol Chem 273: 4027–4034
Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS, Elia A, Pompa JL, Kagi J, Khoo W, Potter J, Yoshida R, Kaufman SA, Lowe SW, Penninger JM and Mak TW (1998) Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 94: 339–352
Hibi M, Lin A, Smeal T, Minden A and Karin M (1993) Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev 7: 2135–2148
Huang Y, Sheikh MS, Fornace AJ Jr and Holbrook NJ (1999) Serine protease inhibitor TPCK prevents Taxol-induced cell death and blocks c-Raf-1 and Bcl-2 phosphorylation in human breast carcinoma cells. Oncogene 18: 3431–3439
Hunter T (1997) Oncoprotein networks. Cell 88: 333–346
Kato H and Torigoe T (1977) Radioimmunoassay for tumour antigen of human cervical squamous cell carcinoma. Cancer 40: 1621–1628
Kato H, Morioka H, Tsutsui H, Aramaki S and Torigoe T (1982) Value of tumour- antigen (TA-4) of squamous cell carcinoma in predicting the extent of cervical cancer. Cancer 50: 1294–1296
Kato H, Tamai K, Morioka H, Nagai M, Nagaya T and Torigoe T (1983) Prognostic significance of the tumour antigen TA-4 in squamous cell carcinoma of the uterine cervix. Am J Obstet Gynecol 145: 350–354
Kato H, Nagaya T and Torigoe T (1984) Heterogeneity of a tumour antigen TA-4 of squamous cell carcinoma in regulation to its appearance in circulation. Gann 75: 433–435
Karin M (1995) The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem 270: 16483–16486
Kerr JFR, Wyllie AH and Currie AR (1972) Apoptosis: basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26: 239–257
Krajewska M, Krajewski S, Epstein JI, Shabaik A, Sauvageot J, Song K, Kitada S and Reed JC (1996) Immunohistochemical analysis of bcl-2, bax, bcl-X, and mcl-1 expression in prostate cancers. Am J Pathol 148: 1567–1576
Kuwano A, Kondo I, Kishi F, Suminami Y and Kato H (1995) Assignment of the squamous cell carcinoma antigen locus (SCC) to 18q21 by in situ hybridization. Genomics 30: 626
Lenczowski JM, Dominguez L, Eder AM, King LB, Zacharchuk CM and Ashwell JD (1997) Lack of a role for Jun kinase and AP-1 in Fas-induced apoptosis. Mol Cell Biol 17: 170–181
Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES and Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/Caspase-9 complex initiates an apoptotic protease cascade. Cell 91: 479–489
Maruo T, Shibata K, Kimura A, Hoshina A and Mochizuki M (1985) Tumour-associated antigen, TA-4, in the monitoring of the effects of therapy for squamous cell carcinoma of the uterine cervix. Cancer 59: 302–308
Mino N, Iio A and Hamamoto K (1988) Availability of tumour-antigen 4 as a marker of squamous cell carcinoma of the lung and other organs. Cancer 62: 730–734
Miyashita T, Krajewski S and Krajewska M (1994) Tumour suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene 9: 1799–1805
Murakami A, Suminami Y, Sakaguchi Y, Nawata S, Numa F, Kishi F and Kato H (2000) Specific detection and quantitation of SCC antigen 1 and SCC antigen 2 mRNAs by fluorescence-based asymmetric semi-nested reverse transcription PCR. Tumour Biol 21: 224–234
Nawata S, Tsunaga N, Numa F, Tanaka T, Nakamura K and Kato H (1995) Serine protease inhibitor activity of recombinant squamous cell carcinoma antigen towards chymotrypsin, as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Electrophoresis 16: 1027–1030
Nawata S, Nakamura K, Tanaka T, Numa F, Suminami Y, Tsunaga N, Kakegawa H, Katsunuma N and Kato H (1997) Electrophoretic analysis of the ‘cross-class’ interaction between novel inhibitory serpin, squamous cell carcinoma antigen-1 and cystein proteinases. Electrophoresis 18: 784–789
Natoli G, Costanzo A, Ianni A, Templeton DJ, Woodgett JR, Balsano C and Levrero M (1995) Activation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent pathway. Science 275: 200–203
Nemoto S, Xiang J, Huang S and Lin A (1998) Induction of apoptosis by SB 202190 through inhibition of p38β mitogen-activated protein kinase. J Biol Chem 273: 16415–16420
Nishina H, Fischer KD, Radvanyi L, Shahinian A, Hakem R, Rubie EA, Bernstein A, Mark TW, Woodgett JR and Penninger JM (1997) Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3. Nature 385: 350–353
Nozawa S, Kojima M, Tukazaki K, Sakayori M, Iizuka R and Kagiyama N (1990) In vitro and in vivo induction of squamous cell carcinoma antigen (SCC) in a uterine cervical cancer cell line (SKG IIIa) with peplomycin and sodium butyrate. Asia-Oceania J Obstet Gynecol 16: 153–160
Numa F, Hirabayashi K, Tsunaga N, Kato H, O’Rourke K, Shao H, Stechmann-Lebakken C, Varani J, Rapraeger A and Dixit VM (1995) Elevated levels of Syndecan-1 expression confer potent serum-dependent growth in human 293T cells. Cancer Res 15: 4676–4680
Park DS, Stefanis L, Yan CYI, Farinelli SE and Greene LA (1996) Ordering the cell death pathway. J Biol Chem 271: 21898–21905
Remold-O’Donnell E (1993) The ovalbumin family of serpin proteins. FEBS Lett 315: 105–108
Roulston A, Reinhard C, Amiri P and Williams LT (1998) Early activation of c-Jun N-terminal kinase and p38 kinase regulate cell survival in response to tumour necrosis factor α. J Biol Chem 273: 10232–10239
Sakaguchi Y, Kishi F, Murakami A, Suminami Y and Kato H (1999) Structural analysis of human SCC antigen 2 promoter. Biochim Biophys Acta 1444: 111–116
Schick C, Kamachi Y, Bartuski AJ, Çataltepe S, Schechter NM, Pemberton PA and Silverman GA (1997) Squamous cell carcinoma antigen 2 is a novel serpin that inhibits the chymotrypsin-like proteinases cathepsin G and mast cell chymase. J Biol Chem 17: 1849–1855
Schick C, Pemberton PA, Shi GP, Kamachi Y, Çataltepe S, Bartuski AJ, Cornstein ER, Brömme D, Chapman HA and Silverman GA (1998) Cross-class inhibition of the cysteine proteinases cathepsin K, L, S by the serpin squamous cell carcinoma antigen 1: A kinetic analysis. Biochemistry 37: 5258–5266
Schneider SS, Schick C, Fish KE, Miller E, Pena JC, Treter SD, Hui SM and Silverman GA (1995) A serine proteinase inhibitor locus at 18q21.3 contains a tandem duplication of the human squamous cell carcinoma antigen gene. Proc Natl Acad Sci USA 92: 3147–3151
Sluss HK, Barrett T, Derijard B and Davis RJ (1994) Signal transduction by tumour necrosis factor mediated by JNK protein kinases. Mol Cell Biol 14: 8376–8384
Suminami Y, Kishi F, Sekiguchi K and Kato H (1991) Squamous cell carcinoma antigen is a new member of the serine protease inhibitors. Biochem Biophys Res Commun 181: 51–58
Suminami Y, Nagashima S, Vujanovic NL, Hirabayashi K, Kato H and Whiteside TL (2000) Inhibition of apoptosis in human tumour cells by the tumour-associated serpin, SCC antigen-1. Br J Cancer 82: 981–989
Takekawa M and Saito H (1998) A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK. Cell 95: 521–530
Takeshima N, Nakamura K, Takeda O, Morioka H, Tamura H, Takasugi N and Kato H (1990) Individualization of the cutoff value for squamous-cell carcinoma antigen using sensitive enzyme immunoassay. Tumour Biol 11: 167–172
Tewari M and Dixit VM (1995) Fas- and tumour necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product. J Biol Chem 270: 3255–3260
Tewari M, Quan LT, O’Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salveson GS and Dixit VM (1995a) Yama/CPP 32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly (ADP-ribose) polymerase. Cell 81: 801–809
Tewari M, Telford WG, Miller RA and Dixit VM (1995b) CrmA, a poxvirus-encoded serpin, inhibits cytotoxic T-lymphocyte-mediated apoptosis. J Biol Chem 270: 22705–22708
Wagenknecht B, Schulz JB, Gulbins E and Weller M (1998) Crm-A, bcl-2 and NDGA inhibit CD95-L-induced apoptosis of malignant glioma cells at the level of caspase 8 processing. Cell Death Diff 5: 894–900
Wyllie AH, Kerr JFR and Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68: 251–306
Xia Z, Dickens M, Raingeaud J, Davis RJ and Greenberg ME (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270: 1326–1331
Yamazaki T and Aoki Y (1998) Cathepsin G enhances human natural killer cytotoxicity. Immunology 93: 115–121
Yang X and Khosravi-Far R Chang HY and Baltimore D (1997) Daxx, a novel Fas-binding protein that activates JNK and apoptosis. Cell 89: 1067–1076
Zhan Q, Fan S, Bae I, Guillof C, Liebermann DA, O’Connor PM and Fornance, Jr AJ (1994) Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis. Oncogene 9: 3743–3751
Zhang J, Gao JX, Salojin K, Shao Q, Grattan M, Meagher C, Laird DW and Delovitch TL (2000) Regulation of Fas ligand expression during activation-induced cell death in T cells by p38 mitogen-activated protein kinase and c-Jun NH2-terminal. J Exp Med 191: 1017–1029
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Murakami, A., Suminami, Y., Hirakawa, H. et al. Squamous cell carcinoma antigen suppresses radiation-induced cell death. Br J Cancer 84, 851–858 (2001). https://doi.org/10.1054/bjoc.2000.1683
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.2000.1683
Keywords
This article is cited by
-
A prognostic model using FIGO 2018 staging and MRI-derived tumor volume to predict long-term outcomes in patients with uterine cervical squamous cell carcinoma who received definitive radiotherapy
World Journal of Surgical Oncology (2023)
-
SERPINB3 (SCCA1) inhibits cathepsin L and lysoptosis, protecting cervical cancer cells from chemoradiation
Communications Biology (2022)
-
Loss of epidermal MCPIP1 is associated with aggressive squamous cell carcinoma
Journal of Experimental & Clinical Cancer Research (2021)
-
Serum conversion pattern of SCC-Ag levels between pre- and post-chemoradiotherapy predicts recurrence and metastasis in cervical cancer: a multi-institutional analysis
Clinical & Experimental Metastasis (2021)
-
Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer
British Journal of Cancer (2018)