High Expression of ABL2 Suppresses Apoptosis in Gastric Cancer

  • Yun Liu
  • Chen Shao
  • Linqi Zhu
  • Sihong Jiang
  • Guanlin Li
  • Wei Zhang
  • Yajing Lin
  • Ying Ni
  • Hui Cao
  • Shihe Shao
Original Article
  • 23 Downloads

Abstract

Background

Diseases associated with Abelson-related gene (also called ABL2) include leukemia; furthermore, previous researches have studied the expressions and functions of ABL2 in different types of malignancies and found that it plays an important role in almost all kinds of cancers.

Aims

Nevertheless, the mechanism of ABL2 in gastric cancer (GC) remains vague.

Methods

In the present study, the level of ABL2 in human GC tissues was detected by immunohistochemistry. Also, the GC cell lines MGC-803 and BGC-823 were selected to stably knock down and overexpress the level of ABL2 by corresponding lentiviral vectors. Puromycin was used to maintain the stable low expression of ABL2 MGC-803 cells compared with control cells; what is more, the high expression of ABL2 BGC-823 cells was also obtained. Based on it, we detected the proteins associated with apoptosis, such as Bcl-2 family and caspase family by western blotting.

Results

The most appropriate concentration of puromycin to kill GC cells is 1 µg/mL; then, we obtained the corresponding stable cell lines. Furthermore, we found that high level of ABL2 in BGC-823 cells increased the expression of Bcl-XL, total PARP, and caspase3, while decreased the level of cleaved caspase3 and cleaved caspase9. Consistent results are received in MGC-803 cells. In addition, ABL2 overexpression led to the protein related with Ras/Erk and PI3K/AKT signaling pathway increased; also, we found that the major proteins play a significant role in it.

Conclusion

All the data showed that high expression of ABL2 suppresses apoptosis through Ras/Erk and PI3K/AKT signaling pathway in GC cell lines.

Keywords

ABL2 Apoptosis Gastric cancer Caspase Bcl-XL 

Notes

Acknowledgments

This work was founded by the National Natural Science Foundation of China (Grant No. 81772157), Natural Science Foundation of Jiangsu Province, China (Grant No. BK20161345), Key Young Medicine Talents of Jiangsu Province (Grant No. QNRC2016457), and Major Program of Natural Science Research in Colleges and Universities of Jiangsu Province in 2017 (Grant No. 17KJA320001).

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

Supplementary material

10620_2018_5111_MOESM1_ESM.docx (381 kb)
Supplementary material 1 (DOCX 380 kb)
10620_2018_5111_MOESM2_ESM.doc (36 kb)
Supplementary material 2 (DOC 35 kb)

References

  1. 1.
    Fang W, Chen Y, Sheng J, et al. Association between PD-L1 expression on tumour-infiltrating lymphocytes and overall survival in patients with gastric cancer. J Cancer. 2017;8:1579–1585.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Fang J, Wang H, Liu Y, Ding F, Ni Y, Shao S. High KRT8 expression promotes tumor progression and metastasis of gastric cancer. Cancer Sci. 2017;108:178–186.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Padmanabhan N, Ushijima T, Tan P. How to stomach an epigenetic insult: the gastric cancer epigenome. Nat Rev Gastroenterol Hepatol. 2017;14:467–478.PubMedGoogle Scholar
  4. 4.
    Dhivya R, Ranjani J, Bowen PK, Rajendhran J, Mayandi J, Annaraj J. Biocompatible curcumin loaded PMMA-PEG/ZnO nanocomposite induce apoptosis and cytotoxicity in human gastric cancer cells. Mater Sci Eng C Mater Biol Appl. 2017;80:59–68.CrossRefPubMedGoogle Scholar
  5. 5.
    Wang J, Pendergast AM. The emerging role of ABL kinases in solid tumors. Trends Cancer. 2015;1:110–123.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Li M, Lin J. The apoptotic pathways and their mechanisms. Guoji Fuchankexue Zazhi. 2014;2:103–107.Google Scholar
  7. 7.
    Liu X, Ji Q, Zhang C, et al. miR-30a acts as a tumor suppressor by double-targeting COX-2 and BCL9 in H. pylori gastric cancer models. Sci Rep. 2017;7:7113.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Sun L, Tu H, Chen T, et al. Three-dimensional combined biomarkers assay could improve diagnostic accuracy for gastric cancer. Sci Rep. 2017;7:11621.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Qin X, Wan Y, Wang S, Xue M. MicroRNA-125a-5p modulates human cervical carcinoma proliferation and migration by targeting ABL2. Drug Des Dev Ther. 2016;10:71–79.Google Scholar
  10. 10.
    Xing QT, Qu CM, Wang G. Overexpression of Abl2 predicts poor prognosis in hepatocellular carcinomas and is associated with cancer cell migration and invasion. Onco Targets Ther. 2014;7:881–885.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Gil-Henn H, Patsialou A, Wang Y, Warren MS, Condeelis JS, Koleske AJ. Arg/Abl2 promotes invasion and attenuates proliferation of breast cancer in vivo. Oncogene. 2013;32:2622–2630.CrossRefPubMedGoogle Scholar
  12. 12.
    Bianchi C, Torsello B, Di Stefano V, et al. One isoform of Arg/Abl2 tyrosine kinase is nuclear and the other seven cytosolic isoforms differently modulate cell morphology, motility and the cytoskeleton. Exp Cell Res. 2013;319:2091–2102.CrossRefPubMedGoogle Scholar
  13. 13.
    Kerrisk ME, Koleske AJ. Arg kinase signaling in dendrite and synapse stabilization pathways: memory, cocaine sensitivity, and stress. Int J Biochem Cell Biol. 2013;45:2496–2500.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Kwon CH, Park HJ, Choi Y, Won YJ, Lee SJ, Park DY. TWIST mediates resistance to paclitaxel by regulating Akt and Bcl-2 expression in gastric cancer cells. Tumour Biol. 2017;39:1010428317722070.PubMedGoogle Scholar
  15. 15.
    Gong H, Lu P, Zhang J, Li D, Zheng J, Song J. Na +/K + ATPase DR region specific antibody protects U251 cells against hypoxia reperfusion induced injury via the PI3K/AKT and ERK pathways. Mol Med Rep. 2017;16:7901–7906.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ji D, Li J. Advances in the treatment of gastric cancer targeting PI3K/Akt/mTOR pathway. TUMOR. 2014;34:191–196.Google Scholar
  17. 17.
    Ji Y, Ji C, Yue L, Xu H. Saponins isolated from Asparagus induce apoptosis in human hepatoma cell line HepG2 through a mitochondrial-mediated pathway. Curr Oncol. 2012;19:eS1–eS9.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Yue Y, Zhang Y, Zhang Y. Caspase family and apoptosis. Natl Med Front China. 2011;6:25–26.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yun Liu
    • 1
  • Chen Shao
    • 2
  • Linqi Zhu
    • 1
  • Sihong Jiang
    • 1
  • Guanlin Li
    • 1
  • Wei Zhang
    • 1
  • Yajing Lin
    • 1
  • Ying Ni
    • 1
  • Hui Cao
    • 1
  • Shihe Shao
    • 1
  1. 1.School of MedicineJiangsu UniversityZhenjiangChina
  2. 2.Department of CardiologyAffiliated Hospital of Jiangsu UniversityZhenjiangChina

Personalised recommendations