Gene expression of ING4 gene in pancreatic cancers and splice forms of ING4 gene

ć°brahim Halil Yıldırım; Ecir Ali í‡akmak; Celaleddin Camcı

doi:10.14715/cmb/2018.64.13.2

Issue

Vol. 64 No. 13: Issue 13

Issue Published : November 2, 2018

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Gene expression of ING4 gene in pancreatic cancers and splice forms of ING4 gene

https://doi.org/10.14715/cmb/2018.64.13.2

ć°brahim Halil Yıldırım

Dicle University, Faculty of Veterinary Medicine, Department of Genetics, Diyarbakır, Türkiye

Ecir Ali í‡akmak

Gaziantep University, Faculty of Medicine, Department of Medical Biology and Genetics, Konya, Türkiye

Celaleddin Camcı

Ethica Private Hospital Medical Oncology, Clinic Bakirkoy, Istanbul, Turkey

Corresponding Author(s) : ć°brahim Halil Yıldırım

ihyildirim@gmail.com

Cellular and Molecular Biology, Vol. 64 No. 13: Issue 13
Article Published : October 30, 2018

Abstract

Pancreatic cancer is characterized by rapid metastasis and resistant to medical treatments. As the other cancers, mutations of tumor suppressor genes that involved in suppression of cell growth are observed in pancreatic cancers. ING4 protein is one of the proteins involved in the regulation of p53 tumor suppressor gene functions. ING4 involved in suppression of cell proliferation, chromosome rearrangement, cell migration, and angiogenesis. In this study, gene expressions and splicing variants of ING4 gene were investigated. Fresh tumor and normal specimens of the same pancreatic cancer patients were used. Gene expression study carried out by calculating the brightness of the bands on agarose gel and splicing variants were detected by direct sequencing. According to the results, three splice forms of ING4 and a decrease in gene expression of ING4 were determined. Splicing type of ING4 affects the translocation of ING4 proteins into the nucleus. To determine the gene expression of each splicing variant, will further clarify the role of ING4 in pancreatic cancers.

Keywords

ING4 Alternative splicing Gene expression p53 Pancreatic cancer.

Yıldırım, ć°brahim H., í‡akmak, E. A., & Camcı, C. (2018). Gene expression of ING4 gene in pancreatic cancers and splice forms of ING4 gene. Cellular and Molecular Biology, 64(13), 6–9. https://doi.org/10.14715/cmb/2018.64.13.2

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References

- Keleg S, Büchler P, Ludwig R, Büchler MW, Friess H, Invasion and metastasis in pancreatic cancer, Molecular Cancer. 2003;2:14, 1-7.
- Pour PM, The silent killer, Int. J. Pancreatology. 1991;10:103-104.
- Pour PM, Pandey KK, Batra SK, What is th eorigin of pancreatic adenocarcinoma. Molecular Cancer. 2003, 2:13.
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- Yu GZ, Genetic alterations and reduced ezpression of tumor supressor p33 in human exocrine pancreatic carcinoma, World J. of Gastroenterology. 2004:10(24), 3597-3601.
- Garkavtsev I, Kazarov A, Gudkov A, Riabowol K, Supression of novel growth inhibitor p33 (ING1) promotes neoplastic transformation, Nat. Gen. 1996;14: 415-420.
- Coles AH, Jones SN, The ING family in the regulation of cell growth and tumorigenesis, J. Cellular Physiology. 2008;218:45-57.
- Pourani J, Kaserer K, Pfragner R, Cytogenetic and molecular analyses of multiple endocrine neoplasias of the MEN1 syndrome, Int. J. Oncol. 2002;20(5): 971-976.
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- Unoki M, Shen JC, Zheng Z, Haris CC, Novel splice variants of ING4 and their possible roles in the regulation of cell growth and motility. J. Biol. Chem. 2006;274:787-789.
- Zhang X, Xu L-S, Wang Z-Q, Wang K-S, Li N, Cheng Z-H, et al. ING4 induces G2/M cell cycle arrest and enhance the chemosensitivity to DNA-dmage agents in HepG2 cells. FEBS Letters. 2004;570: 7-12.
- Li M., Jin Y., Sun W., Yu Y., Bai J., Tong D., et al. Reduced expression and novel spilce variants of ING4 in human gastric adenocarcinoma. Journal of Pathology. 2009;219(1): 87-95.
- Chen Y, Huang Y, Hou P, Zhang Z, Zhang Y, Wang W, et al. ING4 suppresses tumor angiogenesis and functions as a prognostic marker in human colorectal cancer, Oncotarget. 2016;7(48):79017-79031.
- J. Yuan, Y.-L. Han, T.-Y. Wang, S. Wu, L. Tong, L.-X. Lin, M Li, et al. The expression of inhibitor of growth 4 is reduced in cervical cancer tissues, Eur Rev Med Pharmacol Sci, 2016;20(15): 3178-3185.
- Drexler HG, Review of alterations of the cyclin-dependent kinase inhibitor INK4 family gens p15, p16, p18 and p19 in human leukemia-lymhoma cells. Leukemia. 1998;12:845-859.
- Herzog CR, Crist KA, Sabourin CLK, Kellof GJ, Bone CW, Stoner GD, et al. Chormosome 3p tumor-suppressor gene alterations in cervical carcinomas. Molecular Carcinogenesis. 2001;30(3):159-168.
- Meek DW, Tumour suppression by p53: a role fort he DNA damage response? Nature. 2009;9:714-723.
- Kim S, Chin K, Gray JW, Bishop JM, A screen for genes that suppress loos of contact inhibition: Identification of ING4 as a candidate tumor supprressor gene in human cancer. Proc. Natl. Acad. Sci. USA, 2004;101:16251-16256.
- Zhang X, Wang K, Wang Z, Xu L, Wang Q, Chen F, et al. Nuclear localization signals of ING4 plays a key role in its binding to p53. Biochem. Biphhysc. Res. Comm. 2005;331:1032-1038.
- Prives C, Manfredi JJ, The p53 tumor suppressor protein: meeting review. Genes Dev. 1993;7:529-534.
- Soliman MA, Riabowol K., After a decade of study-ING, a PHD for a versatile family of proteins. Trends in Biochemical Sciences. 2007;32 (11): 509-519.
- Ho CW, Fitzgerald MX, Marmorstein R, Structure of the p53 core domain dimer bound to DNA, J. Biological Chem. 2006;281:20494-20502.
- Velculescu VE, El-Deiry WS, Biological and clinical importance of the p53 tumor suppressor gene. Clinical Chemistry. 1996;42(6):858-868.
- í–zkul Y, Jurickova I, Findley HW, Variable expression and hypermethylation of p16 gene in patients with T-ALL and cell lines. Turk J. Haematol. 2002;19(3):391-397.

References

- Keleg S, Büchler P, Ludwig R, Büchler MW, Friess H, Invasion and metastasis in pancreatic cancer, Molecular Cancer. 2003;2:14, 1-7.

- Pour PM, The silent killer, Int. J. Pancreatology. 1991;10:103-104.

- Pour PM, Pandey KK, Batra SK, What is th eorigin of pancreatic adenocarcinoma. Molecular Cancer. 2003, 2:13.

- Nakamori S, Yashima K, Murakami Y, Association of p53 gene mutations with short survival in pancreatic adenocarcinoma. Japan J. Cancer Res. 1995;86:174-181.

- Yu GZ, Genetic alterations and reduced ezpression of tumor supressor p33 in human exocrine pancreatic carcinoma, World J. of Gastroenterology. 2004:10(24), 3597-3601.

- Garkavtsev I, Kazarov A, Gudkov A, Riabowol K, Supression of novel growth inhibitor p33 (ING1) promotes neoplastic transformation, Nat. Gen. 1996;14: 415-420.

- Coles AH, Jones SN, The ING family in the regulation of cell growth and tumorigenesis, J. Cellular Physiology. 2008;218:45-57.

- Pourani J, Kaserer K, Pfragner R, Cytogenetic and molecular analyses of multiple endocrine neoplasias of the MEN1 syndrome, Int. J. Oncol. 2002;20(5): 971-976.

- Gunduz M, Nagatsuka H, Demircan K, Gunduz E, Cengiz B, Ouchida M, et al. Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas. Gene. 2005;356: 109-117.

- Unoki M, Shen JC, Zheng Z, Haris CC, Novel splice variants of ING4 and their possible roles in the regulation of cell growth and motility. J. Biol. Chem. 2006;274:787-789.

- Zhang X, Xu L-S, Wang Z-Q, Wang K-S, Li N, Cheng Z-H, et al. ING4 induces G2/M cell cycle arrest and enhance the chemosensitivity to DNA-dmage agents in HepG2 cells. FEBS Letters. 2004;570: 7-12.

- Li M., Jin Y., Sun W., Yu Y., Bai J., Tong D., et al. Reduced expression and novel spilce variants of ING4 in human gastric adenocarcinoma. Journal of Pathology. 2009;219(1): 87-95.

- Chen Y, Huang Y, Hou P, Zhang Z, Zhang Y, Wang W, et al. ING4 suppresses tumor angiogenesis and functions as a prognostic marker in human colorectal cancer, Oncotarget. 2016;7(48):79017-79031.

- J. Yuan, Y.-L. Han, T.-Y. Wang, S. Wu, L. Tong, L.-X. Lin, M Li, et al. The expression of inhibitor of growth 4 is reduced in cervical cancer tissues, Eur Rev Med Pharmacol Sci, 2016;20(15): 3178-3185.

- Drexler HG, Review of alterations of the cyclin-dependent kinase inhibitor INK4 family gens p15, p16, p18 and p19 in human leukemia-lymhoma cells. Leukemia. 1998;12:845-859.

- Herzog CR, Crist KA, Sabourin CLK, Kellof GJ, Bone CW, Stoner GD, et al. Chormosome 3p tumor-suppressor gene alterations in cervical carcinomas. Molecular Carcinogenesis. 2001;30(3):159-168.

- Meek DW, Tumour suppression by p53: a role fort he DNA damage response? Nature. 2009;9:714-723.

- Kim S, Chin K, Gray JW, Bishop JM, A screen for genes that suppress loos of contact inhibition: Identification of ING4 as a candidate tumor supprressor gene in human cancer. Proc. Natl. Acad. Sci. USA, 2004;101:16251-16256.

- Zhang X, Wang K, Wang Z, Xu L, Wang Q, Chen F, et al. Nuclear localization signals of ING4 plays a key role in its binding to p53. Biochem. Biphhysc. Res. Comm. 2005;331:1032-1038.

- Prives C, Manfredi JJ, The p53 tumor suppressor protein: meeting review. Genes Dev. 1993;7:529-534.

- Soliman MA, Riabowol K., After a decade of study-ING, a PHD for a versatile family of proteins. Trends in Biochemical Sciences. 2007;32 (11): 509-519.

- Ho CW, Fitzgerald MX, Marmorstein R, Structure of the p53 core domain dimer bound to DNA, J. Biological Chem. 2006;281:20494-20502.

- Velculescu VE, El-Deiry WS, Biological and clinical importance of the p53 tumor suppressor gene. Clinical Chemistry. 1996;42(6):858-868.

- í–zkul Y, Jurickova I, Findley HW, Variable expression and hypermethylation of p16 gene in patients with T-ALL and cell lines. Turk J. Haematol. 2002;19(3):391-397.

Author biographies is not available.