Growth factor signaling plays a key role in the growth and development of breast. Aberrant expression and activation of growth factors like insulin like growth factor-I (IGF-I) and epidermal growth factor (EGF) and their downstream sig naling has been implicated in breast cancer. The deregulation of growth factor signaling is associated with increased proliferation and cell survival, decreased apoptosis, invasion, angiogenesis and metastasis. The aim of the present study is to survey the different signaling molecules involved in the IGF and EGF signaling pathways, and to find if there are any relationship between breast cancer and their levels and activation. Thirty - nine samples of breast cancer tissues (24 Grade II and 15 Grade III tumours) and sixteen normal breast tissue samples were collected. The expression of the re ceptors and signaling molecules were investigated using Western blot. IGF-IR β , AR, pAkt, IKK- α and p38 are upregu lated in cancer tissues in a grade depended manner. Further, Akt and β -catenin were also upregulated in cancer samples. Correlation analysis of signaling molecules revealed a disruption in their expression in cancer tissues. The present study shows that various signaling molecules are upregulated or activated in cancer tissues involving IGF-IR and Akt path way. The expression of signaling molecules in the cancer tissues were deregulated when compared to the control sam ples. Thus, flawed expression and over activation of Akt pathway is seen in the breast cancer tissues.
E. Marshman and C. H. Streuli, “Insulin-Like Growth Factors and Insulin-Like Growth Factor Binding Proteins in Mammary Gland Function,” Breast Cancer Research: BCR, Vol. 4, 2002, pp. 231-239. doi:10.1186/bcr535
W. Ruan, V. Catanese, R. Wieczorek, M. Feldman and D. L. Kleinberg, “Estradiol Enhances the Stimulatory Effect of Insulin-Like Growth Factor-I (IGF-I) on Mammary Development and Growth Hormone-Induced IGF-I Messenger Ribonucleic Acid,” Endocrinology, Vol. 136, No. 3, 1995, pp. 1296-302. doi:10.1210/en.136.3.1296
H. M. Khandwala, I. E. McCutcheon, A. Flyvbjerg and K. E. Friend, “The Effects of Insulin-Like Growth Factors on Tumorigenesis and Neoplastic Growth,” Endocrine ReViews, Vol. 21, No. 3, 2000, pp. 215-244. doi:10.1210/er.21.3.215
M. Pollak, “Insulin-Like Growth Factor Physiology and Cancer Risk,” European Journal of Cancer, Vol. 36, 2000, pp. 1224-1228. doi:10.1016/S0959-8049(00)00102-7
A. Ouban, P. Muraca, T. Yeatman and D. Coppola, “Expression and Distribution of Insulin-Like Growth Factor-1 Receptor in Human Carcinomas,” Human Pathology, Vol. 34, No. 8, 2003, pp. 803-808. doi:10.1016/S0046-8177(03)00291-0
P. O. Hackel, E. Zwick, N. Prenzel and A. Ullrich, “Epidermal Growth Factor Receptors: Critical Mediators of Multiple Receptor Pathways,” Current Opinion in Cell Biology, Vol. 11, No. 2, 1999, pp. 184-189. doi:10.1016/S0955-0674(99)80024-6
H. W. Lo, S. C. Hsu, W. Xia, X. Cao, J. Y. Shih, et al., “Epidermal Growth Factor Receptor Cooperates with Signal Transducer and Activator of Transcription 3 to Induce Epithelial-Mesenchymal Transition in Cancer Cells via Up-Regulation of TWIST Gene Expression,” Cancer ReSearch, Vol. 67, No. 19, 2007, pp. 9066-9076. doi:10.1158/0008-5472.CAN-07-0575
Q. Ding, X. He, W. Xia, J. M. Hsu, C. T. Chen, et al., “Myeloid Cell Leukemia-1 Inversely Correlates with Glycogen Synthase Kinase-3Beta Activity and Associates with Poor Prognosis in Human Breast Cancer,” Cancer Research, Vol. 67, No. 10, 2007, pp. 4564-4571. doi:10.1158/0008-5472.CAN-06-1788
S. Y. Lin, W. Xia, J. C. Wang, K. Y. Kwong, B. Spohn, et al., “Beta-Catenin, a Novel Prognostic Marker for Breast Cancer: Its Roles in Cyclin D1 Expression and Cancer Progression,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 8, 2000, pp. 4262-4266. doi:10.1073/pnas.060025397
T. P. Garrington and G. L. Johnson, “Organization and Regulation of Mitogen-Activated Protein Kinase Signaling Pathways,” Current Opinion in Cell Biology, Vol. 11, No. 2, 1999, pp. 211-218. doi:10.1016/S0955-0674(99)80028-3
V. S. Sivaraman, H. Wang, G. J. Nuovo and C. C. Malbon, “Hyperexpression of Mitogen-Activated Protein Kinase in Human Breast Cancer,” The Journal of Clinical Investigation, Vol. 99, No. 7, 1997, pp. 1478-1483. doi:10.1172/JCI119309
F. Houle and J. Huot, “Dysregulation of the Endothelial Cellular Response to Oxidative Stress in Cancer,” Molecular Carcinogenesis, Vol. 45, No. 6, 2006, pp. 362-367. doi:10.1002/mc.20218
Y. Cao and M. Karin, “NF-KappaB in Mammary Gland Development and Breast Cancer,” Journal of Mammary Gland Biology and Neoplasia, Vol. 8, No. 2, 2003, pp. 215-223. doi:10.1023/A:1025905008934
O. J. Finn, “Cancer Immunology,” The New England Journal of Medicine, Vol. 358, No. 25, 2008, pp. 2704-2715. doi:10.1056/NEJMra072739
D. Yee and A. V. Lee, “Crosstalk between the InsulinLike Growth Factors and Estrogens in Breast Cancer,” Journal of Mammary Gland Biology and Neoplasia, Vol. 5, No. 1, 2000, pp. 107-115. doi:10.1023/A:1009575518338
W. Schippinger, P. Regitnig, N. Dandachi, K. D. Wernecke, T. Bauernhofer, et al., “Evaluation of the Prognostic Significance of Androgen Receptor Expression in Metastatic Breast Cancer,” Virchows Archiv: An International Journal of Pathology, Vol. 449, No. 1, 2006, pp. 24-30.
E. O. Lillie, L. Bernstein and G. Ursin, “The Role of Androgens and Polymorphisms in the Androgen Receptor in the Epidemiology of Breast Cancer,” Breast Cancer ReSearch: BCR, Vol. 5, No. 3, 2003, pp. 164-173. doi:10.1186/bcr593
K. Hanley, J. Wang, P. Bourne, Q. Yang, A. C. Gao, et al., “Lack of Expression of Androgen Receptor May Play a Critical Role in Transformation from in Situ to Invasive Basal Subtype of High-Grade Ductal Carcinoma of the Breast,” Human Pathology, Vol. 39, 2008, pp. 386-392. doi:10.1016/j.humpath.2007.07.007
M. N. Pollak, E. S. Schernhammer and S. E. Hankinson, “Insulin-Like Growth Factors and Neoplasia,” Nature Reviews. Cancer, Vol. 4, No. 7, 2004, pp. 505-518. doi:10.1038/nrc1387
L. Mack, N. Kerkvliet, G. Doig and F. P. O’Malley, “Relationship of a New Histological Categorization of Ductal Carcinoma in Situ of the Breast with Size and the Immunohistochemical Expression of p53, c-erb B2, bcl-2, and ki-67,” Human Pathology, Vol. 28, No. 8, 1997, pp. 974-979. doi:10.1016/S0046-8177(97)90014-9
L. P. Kane, M. N. Mollenauer, Z. Xu, C. W. Turck and A. Weiss, “Akt-Dependent Phosphorylation Specifically Regulates Cot Induction of NF-Kappa B-Dependent Transcription,” Molecular and Cellular Biology, Vol. 22, No. 16, 2002, pp. 5962-5974. doi:10.1128/MCB.22.16.5962-5974.2002
G. Gasparini, P. Boracchi, P. Bevilacqua, M. Mezzetti, F. Pozza and N. Weidner, “A Multiparametric Study on the Prognostic Value of Epidermal Growth Factor Receptor in Operable Breast Carcinom A,” Breast Cancer Research and Treatment, Vol. 29, No. 1, 1994, pp. 59-71. doi:10.1007/BF00666182
S. Frame and P. Cohen, “GSK3 Takes Centre Stage More than 20 Years after Its Discovery,” The Biochemical Journal, Vol. 359, No. 1, 2001, pp. 1-16. doi:10.1042/0264-6021:3590001
G. G. Chung, M. P. Zerkowski, I. T. Ocal, M. DolledFilhart, J. Y. Kang, et al., “Beta-Catenin and p53 Analyses of a Breast Carcinoma Tissue Microarray,” Cancer, Vol. 100, No. 10, 2004, pp. 2084-2092. doi:10.1002/cncr.20232
T. M. Thornton and M. Rincon, “Non-Classical p38 Map Kinase Functions: Cell Cycle Checkpoints and Survival,” International Journal of Biological Sciences, Vol. 5, No. 1, 2009, pp. 44-51.
K. L. Mueller, K. Powell, J. M. Madden, S. T. Eblen and J. L. Boerner, “EGFR Tyrosine 845 Phosphorylation-Dependent Proliferation and Transformation of Breast Cancer Cells Require Activation of p38 MAPK,” Translational Oncology, Vol. 5, No. 5, 2012, pp. 327-334.
E. F. Wagner and A. R. Nebreda, “Signal Integration by JNK and p38 MAPK Pathways in Cancer Development,” Nature Reviews. Cancer, Vol. 9, No. 8, 2009, pp. 537-549. doi:10.1038/nrc2694
J. M. Renoir, V. Marsaud and G. Lazennec, “Estrogen Receptor Signaling as a Target for Novel Breast Cancer Therapeutics,” Biochemical Pharmacology, Vol. 85, No. 4, 2013, pp. 449-465.
J. P. Garay, B. Karakas, A. M. Abukhdeir, D. P. Cosgrove, J. P. Gustin, et al., “The Growth Response to Androgen Receptor Signaling in ERalpha-Negative Human Breast Cells Is Dependent on p21 and Mediated by MAPK Activation,” Breast Cancer Research: BCR, Vol. 14, No. 1, 2012, p. R27. doi:10.1186/bcr3112
R. Klopfleisch and A. D. Gruber, “Differential Expression of Cell Cycle Regulators p21, p27 and p53 in Metastasizing Canine Mammary Adenocarcinomas versus Normal Mammary Glands,” Research in Veterinary Science, Vol. 87, No. 1, 2009, pp. 91-96. doi:10.1016/j.rvsc.2008.12.010