Effects of 4-(3-Chloro-Benzyl)-6,7-Dimethoxy-Quinazoline on Kinetics of P120-Catenin and Periplakin in Human Buccal Mucosa Squamous Carcinoma Cell Line


In order to detect molecular markers for the epidermal growth factor inhibitor 4-(3-chloro-benzyl)- 6,7-dimethoxy-quinazoline (tyrphostin), we investigated the kinetics of p120-catenin and periplakin in the human buccal mucosa squamous cancer cell line BICR 10 treated with 3 nM tyrphostin. Growth of BICR 10 cells was inhibited by treatment with tyrphostin. Although changes were not observed in the expression of EGFR and p120-catenin, expression of Akt, Src and periplakin in BICR 10 treated with 3 nM tyrphostin tended to decrease. In addition, phosphorylation of EGFR, Akt and Src was inhibited by treatment with tyrphostin. On immunocytochemical staining, immunoreactions with phosphorylated EGFR, phosphorylated Akt and phosphorylated p120-catenin were weak in BICR 10 treated with tyrphostin. There was a slight immunocy to chemical reaction to periplakin in BICR 10 cells induced by tyrphostin. In conclusion, the decrease in phosphorylation in EGFR and p120-catenin by tyrphostin, following the decrease in Src or Akt phosphorylation, may inhibit expression of several growth factors associated with the proliferation and migration of cancer cells.

Share and Cite:

Tamura, I. , Kamada, A. , Goda, S. , Yoshikawa, Y. , Domae, E. and Ikeo, T. (2014) Effects of 4-(3-Chloro-Benzyl)-6,7-Dimethoxy-Quinazoline on Kinetics of P120-Catenin and Periplakin in Human Buccal Mucosa Squamous Carcinoma Cell Line. Open Journal of Stomatology, 4, 249-257. doi: 10.4236/ojst.2014.45035.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] O-Charoenrat, P., Modjtahedi, H., Evans, P.R., Court, W.J., Box, G.M. and Eccles, S.A. (2000) Epidermal Growth Factor-Like Ligands Differentially Up-Regulate Matrix Metalloproteinase 9 in Head and Neck Squamous Carcinoma Cells. Cancer Research, 60, 1121-1128.
[2] Chothia, C. and Jones, E.Y. (1997) The Molecular Structure of Cell Adhesion Molecules. Annual Review of Biochemistry, 66, 823-862.
[3] Pece, S. and Gutkind, J.S. (2000) Signaling from E-Cadherins to the MAPK Pathway by the Recruitment and Activation of Epidermal Growth Factor Receptors upon Cell-Cell Contact Formation. The Journal of Biological Chemistry, 275, 41227-41233.
[4] Dumstrei, K., Wang, F., Shy, D., Tepass, U. and Hartenstein, V. (2002) Interaction between EGFR Signaling and DE-Cadherin during Nervous System Morphogenesis. Development, 129, 3983-3994.
[5] Chaiken, M.F., Hein, P.W., Stewart, J.C., Brackenbury, R. and Kinch, M.S. (2003) E-Cadherin Binding Modulates EGF Receptor Activation. Cell Communication and Adhesion, 10, 105-118.
[6] Qian, X., Karpova, T., Sheppard, A.M., McNally, J. and Lowy, D.R. (2004) E-Cadherin-Mediated Adhesion Inhibits Ligand-Dependent Activation of Diverse Receptor Tyrosine Kinases. EMBO Journal, 23, 1739-1748.
[7] Takahashi, K. and Suzuki, K. (1996) Density-Dependent Inhibition of Growth Involves Prevention of EGF Receptor Activation by E-Cadherin-Mediated Cell-Cell Adhesion. Experimental Cell Research, 226, 214-222.
[8] Lilien, J., Balsamo, J., Arregui, C. and Xu, G. (2002) Turn-Off, Drop-Out: Functional State Switching of Cadherins. Developmental Dynamics, 224, 18-29.
[9] Yamada, S., Pokutta, S., Drees, F., Weis, W.I. and Nelson, W.J. (2005) Deconstructing the Cadherin-Catenin-Actin Complex. Cell, 123, 889-901.
[10] Wildenberg, G.A., Dohn, M.R., Carnahan, R.H., Davis, M.A., Lobdell, N.A., Settleman, J. and Reynolds, A.B. (2006) P120-Catenin and p190RhoGAP Regulate Cell-Cell Adhesion by Coordinating Antagonism between Rac and Rho. Cell, 127, 1027-1039.
[11] Mariner, D.J., Davis, M.A. and Reynolds, A.B. (2004) EGFR Signaling to p120-Catenin through Phosphorylation at Y228. Journal of Cell Science, 117, 1339-1350.
[12] Ruhrberg, C., Hajibagheri, M.A.N., Parry, D.A.D. and Watt, F.M. (1997) Periplakin, a Novel Component of Cornified Envelopes and Desmosomes That Belongs to the Plakin Family and Froms Complexes with Envoplakin. The Journal of Cell Biology, 139, 1835-1849.
[13] Sonnenberg, A. and Liem, R.K.H. (2007) Plakins in Development and Disease. Experimental Cell Research, 313, 2189-2203.
[14] Boczonadi, V., McInroy, L. and Määttä, A. (2007) Cytolinker Cross-Talk: Periplakin N-Terminus Interacts with Plectin to Regulate Keratin Organization and Epithelial Migration. Experimental Cell Research, 313, 3579-3591.
[15] Nishimori, T., Tomonaga, T., Matsushita, K., Oh-Ishi, M., Kodera, Y., Maeda, T., Nomura, F., Matsubara, H., Shimada, H. and Ochiai, T. (2006) Proteomic Analysis of Primary Esophageal Squamous Cell Carcinoma Reveals Downregulation of a Cell Adhesion Protein, Periplakin. Proteomics, 6, 1011-1018.
[16] Lee, M.F., Chan, C.Y., Hung, H.C., Chou, I.T., Yee, A.S. and Huang, C.Y. (2013) N-Acetylcysteine (NAC) Inhibits Cell Growth by Mediating the EGFR/Akt/HMG Box-Containing Protein 1 (HBP1) Signaling Pathway in Invasive Oral Cancer. Oral Oncology, 49, 129-135.
[17] Lauand, C., Teixeira, P.R., Cortez, B.A., de Oliveira Niero, E.L. and Santelli, G.M.M. (2013) Independent of ErbB1 Gene Copy Number, EGF Stimulates Migration but Is Not Associated with Cell Proliferation in Non-Small Cell Lung Cancer. Cancer Cell International, 13, 38-52.
[18] Edington, K.G., Loughran, O.P., Berry, I.J. and Parkinson, E.K. (1995) Cellular Immortality: A Late Event in the Progression of Human Squamous Cell Carcinoma of the Head and Neck Associated with p53 Alteration and a High Frequency of Allele Loss. Molecular Carcinogenesis, 13, 254-265.
[19] Towbin, H., Staehelin, T. and Gordon, J. (1979) Electrophoretic Transfer of Proteins from Polyacrylamide Gels to Nitrocellulose Sheets: Procedure and Some Applications. Proceedings of the National Academy of Sciences of the United States of America, 76, 4350-4354.
[20] Shi, Z.R., Itzkowitz, S.H. and Kim, Y.S. (1988) A Comparison of Three Immunoperoxidase Techniques for Antigen Detection in Colorectal Carcinoma Tissues. Journal of Histochemistry & Cytochemistry, 36, 317-322.
[21] Tamura, I., Sakaki, T., Chaqour, B., Howard, P.S., Ikeo, T. and Macarak, E.J. (2003) Correlation of P-Cadherin and β-Catenin Expression and Phosphorylation with Carcinogenesis in Rat Tongue Cancer Induced with 4-Nitroquinoline 1-Oxide. Oral Oncology, 39, 506-514.
[22] Fontanini, G., De Laurentiis, M., Silvana Vignati, S., Chinè, S., Lucchi, M., Silvestri, V., Mussi, A., De Placido, S., Tortora, G., Bianco, A.R., Gullick, W., Angeletti, C.A., Bevilacqua, G. and Ciardiello, F. (1998) Evaluation of Epidermal Growth Factor-Related Growth Factors and Receptors and of Neoangiogenesis in Completely Resected Stage I-IIIA Non-Small-Cell Lung Cancer: Amphiregulin and Microvessel Count Are Independent Prognostic Indicators of Survival. Clinical Cancer Research, 4, 241-249.
[23] Moiseeva, E.P., Heukers, R. and Manson, M.M. (2007) EGFR and Src Are Involved in In-dole-3-Carbinol-Induced Death and Cell Cycle Arrest of Human Breast Cancer Cells. Carcinogenesis, 28, 435-445.
[24] Leu, T.H. and Maa, M.C. (2003) Functional Implication of the Interaction between EGF Receptor and C-Src. Frontiers in Bioscience, 8, s28-s38.
[25] Barnes, C.J., Yarmand, R.B., Mandal, M., Yang, Z., Clayman, G.L., Hong, W.K. and Kumar, R. (2003) Suppression of Epidermal Growth Factor Receptor, Mitogen-Activated Protein Kinase, and Pak1 Pathways and Invasiveness of Human Cutaneous Squamous Cancer Cells by the Tyrosine Kinase Inhibitor ZD1839 (Iressa). Molecular Cancer Therapeutics, 2, 345-351.
[26] Itoh, N., Semba, S., Ito, M., Takeda, H., Kawata, S. and Yamakawa, M. (2002) Phosphorylation of Akt/PKB Is Required for Suppression of Cancer Cell Apoptosis and Tumor Progression in Human Colorectal Carcinoma. Cancer, 94, 3127-3134.
[27] Basavaraj, C., Sierra, P., Shivu, J., Melarkode, R., Montero, E. and Nair, P. (2010) Nimotuzumab with Chemoradiation Confers a Survival Advantage in Treatment-Naïve Head and Neck Tumors over Expressing EGFR. Cancer Biology & Therapy, 10, 673-681.
[28] Maseki, S., Ijichi, K., Tanaka, H., Fujii, M., Hasegawa, Y., Ogawa, T., Murakami, S., Kondo, E. and Nakanishi, H. (2012) Acquisition of EMT Phenotype in the Gefitinib-Resistant Cells of a Head and Neck Squamous Cell Carcinoma Cell Line through Akt/GSK-3 Snail Signaling Pathway. British Journal of Cancer, 106, 1196-1204.
[29] Black, P.C., Brown, G.A., Inamoto, T., Shrader, M., Arora, A., Radtke, A.O.S., Adam, L., Theodorescu, D., Wu, X., Munsell, M.F., Eli, M.B., McConkey, D.J. and Dinney, C.P.N. (2008) Sensitivity to Epidermal Growth Factor Receptor Inhibitor Requires E-Cadherin Expression in Urothelial Carcinoma Cells. Clinical Cancer Research, 14, 1478-1486.
[30] Xu, Z.H., Hang, J.B., Hu, J.A. and Gao, B.L. (2013) RAF1-MEK1-ERK/AKT Axis May Confer NSCLC Cell Lines Resistance to Erlotinib. International Journal of Clinical and Experimental Pathology, 6, 1493-1504.
[31] Zang, J., Kalyankrishna, S., Wislez, M., Thilaganathan, N., Saigal, B., Wei, W., Ma, L., Wistuba, I.I., Johnson, F.M. and Kurie, J.M. (2007) Src-Family Kinases Are Activated in Non-Small Cell Lung Cancer and Promote the Survival of Epidermal Growth Factor Receptor-Dependent Cell Lines. American Journal of Pathology, 170, 366-376.
[32] Lee, C.H., Hung, H.W., Hung, P.H. and Shieh, Y.S. (2010) Epidermal Growth Factor Receptor Regulates β-Catenin Location, Stability, and Transcriptional Activity in Oral Cancer. Molecular Cancer, 9, 64-75.
[33] Ma, L.W., Zhou, Z.T., He, Q.B. and Jiang, W.W. (2012) Phosphorylated p120-Catenin Expression Has Predictive Value for Oral Cancer Progression. Journal of Clinical Pathology, 65, 315-319.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.