Tubb3 regulation by the Erk and Akt signaling pathways: a mechanism involved in the effect of arginine ADP-ribosyltransferase 1 (Art1) on apoptosis of colon carcinoma CT26 cells
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The influence of the most important classical mono-ADP-ribosyltransferase, arginine ADP-ribosyltransferase 1 (Art1), on survival and apoptosis of colon carcinoma cells and the potential mechanisms have been partly discussed in our previous study but still need to be further studied. In this present study, Art1 of colon carcinoma CT26 cells was silenced with lentiviral vector-mediated short hairpin RNA (shRNA) or overexpressed with lentiviral vector-mediated complementary DNA (cDNA) and allograft transplant tumors are established in Balb/c mice. We verified Art1 knockdown increases apoptosis of CT26 cells transplant tumor; Art1 overexpression acts oppositely. Accordingly, growth of transplant tumors is inhibited in Art1 knockdown transplant tumors and increases in Art1 overexpression transplant tumors. Furthermore, activity of Akt and Erk cell signal pathways and expression of an apoptosis biomarker, βIII-tubulin (Tubb3), decrease when Art1 was silenced and increase when Art1 was overexpressed. Inhibiting Akt pathway or Erk pathway both downregulates expression of Tubb3 on protein and messenger RNA (mRNA) level, indicating that Tubb3 could be regulated by both Akt and Erk pathways, and plays a role in the influence of Art1 on apoptosis of Balb/c mice allograft transplant tumor. We also demonstrated that Bcl-2 family is not the responsible downstream factor of the Erk pathway in colon carcinoma cells which is undergoing apoptosis. These findings enrich the molecular mechanism for the function of Art1 in colon carcinoma and provide a complementary support for Art1 to be a potential therapeutic target of the treatment of this kind of malignant tumor.
KeywordsTubb3 Art1 Akt Erk Apoptosis
This research was supported by Project Supported by Scientific and Technological Research Program of Chongqing Municipal Education Commission (Grant No. KJ110322) and the Ministry of Education Specialized Research Fund for the Doctoral Program of Higher Education (Grant No. 20105503110009).
Conflicts of interest
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