Document Type : Original Article
Authors
1 Assistant Professor, Department of Biology, Faculty of Sciences, Arak University, Arak, Iran.
2 MSc. Student, Department of Biology, Faulty of Sciences, Arak University, Arak, Iran.
Abstract
Backgrounds Breast cancer is the most common cancer in females worldwide. Phosphatidylinositol 3-kinases (PI3Ks) evolve from lipid kinase that regulates the diverse cellular signaling pathways and are often altered in human cancers. Mutations in the gene encoding the p110α catalytic subunit PI3K (PIK3CA) can increase the enzyme activity and cause uncontrolled growth in cells. Previous studies indicated high frequency of mutation in PIK3CA gene in breast cancer. The current study aimed at determining the activating mutations of PI3K gene that can treat breast cancer using kinase activity of the enzyme inhibitors.
Methods & Materials In the current study, due to the high rate of breast cancer in Markazi province, mutations of PIK3CA gene in 45 patient samples and 20 controls were investigated by the means of single-strand conformational polymorphism (SSCP) and direct DNA sequencing. In addition, the correlation between PIK3CA mutations and clinicopathological factors including age at diagnosis, lymph node metastases, subtype histology, tumor size, and histological grade were investigated by the Pearson Chisquare (X2) test.
Results Among the 26.6% PIK3CA gene mutations in the study, 75% were identified in the exon 9; and accordingly, in addition to hotspot mutation [G1624A (E542K)], another mutation [G1634C (E545A)] was also detected. The current study showed no significant correlation between PIK3CA mutations and clinicopathological factors.
Conclusion Mutations in PI3K gene, a proto-oncogene, showed the importance of this pathway for therapeutic purposes to prevent and cease the growth of breast cancer
Keywords
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: A Cancer Journal for Clinicians. 2011; 61(2):69–90. doi: 10.3322/caac.20107
Sadjadi A, Nouraie M, Mohagheghi MA, Mousavi-Jarrahi A, Malekezadeh R, Donald Maxwell P. Cancer occurrence in Iran in 2002, an international perspective. Asian Pacific Journal of Cancer Prevention. 2005; 6(3):359.
Mohaghegh F, Hamta A. [The study of cancer incidence and cancer registration in Markazi province between 2001-2006 and comparison with national statistics, Iran (Persian)]. Arak Medical University Journal. 2008; 11(2):84-93.
Foster FM. The phosphoinositide (PI) 3-kinase family. Journal of Cell Science. The Company of Biologists; 2003; 116(15):3037–40. doi: 10.1242/jcs.00609
Ligresti G, Militello L, Steelman LS, Cavallaro A, Basile F, Nicoletti F, et al. PIK3CA mutations in human solid tumors: Role in sensitivity to various therapeutic approaches. Cell Cycle. 2009; 8(9):1352–8. doi: 10.4161/cc.8.9.8255
Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase–AKT pathway in human cancer. Nature Reviews Cancer. 2002; 2(7):489–501. doi: 10.1038/nrc839
Akinleye A, Avvaru P, Furqan M, Song Y, Liu D. Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics. Journal of Hematology & Oncology. 2013; 6(1):88. doi: 10.1186/1756-8722-6-88
L Troxell M. PIK3CA/AKT1 Mutations in Breast Carcinoma: a Comprehensive Review of Experimental and Clinical Studies. Journal of Clinical & Experimental Pathology. 2012; 2(S1):002. doi: 10.4172/2161-0681.s1-002
Bachman KE, Argani P, Samuels Y, Silliman N, Ptak J, Szabo S, et al. The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biology & Therapy. Informa UK Limited. 2004; 3(8):772–5. doi: 10.4161/cbt.3.8.994
Samuels Y, Diaz LA, Schmidt-Kittler O, Cummins JM, DeLong L, Cheong I, et al. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell. 2005; 7(6):561–73. doi: 10.1016/j.ccr.2005.05.014
Miller TW. Initiating breast cancer by PIK3CA mutation. Breast Cancer Research. 2012; 14(1). doi: 10.1186/bcr3103
Levine DA. Frequent mutation of the PIK3CA gene in ovarian and breast cancers. Clinical Cancer Research. 2005; 11(8):2875–8. doi: 10.1158/1078-0432.ccr-04-2142
Cizkova M, Susini A, Vacher S, Cizeron-Clairac G, Andrieu C, Driouch K, et al. PIK3CA mutation impact on survival in breast cancer patients and in ERα, PR and ERBB2-based subgroups. Breast Cancer Research. 2012; 14:R28. doi: 10.1186/bcr3113
Campbell IG. Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Research. 2004; 64(21):7678–81. doi: 10.1158/0008-5472.can-04-2933
Liang X, Lau QC, Salto-Tellez M, Putti TC, Loh M, Sukumar S. Mutational hotspot in Exon 20 of PIK3CA in breast cancer among Singapore Chinese. Cancer Biology & Therapy. 2006; 5(5):544–8. doi: 10.4161/cbt.5.5.2656
Barbareschi M, Buttitta F, Felicioni L, Cotrupi S, Barassi F, Del Grammastro M, et al. Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas. Clinical Cancer Research. 2007; 13(2
)