TY - JOUR
T1 - Transglutaminase 2 inhibition found to induce p53 mediated apoptosis in renal cell carcinoma
AU - Ku, Bo Mi
AU - Kim, Dae Seok
AU - Kim, Kyung Hee
AU - Yoo, Byong Chul
AU - Kim, Seok Hyun
AU - Gong, Young Dae
AU - Kim, Soo Youl
PY - 2013/9
Y1 - 2013/9
N2 - Renal cell carcinoma (RCC), the predominant form of kidney cancer, is characterized by high resistance to radiation and chemotherapy. This study shows that expression of protein cross-linking enzyme transglutaminase 2 (TGase 2) is markedly increased in 7 renal cell carcinoma (RCC) cell lines in comparison to HEK293 and other cancer cell lines, such as NCI 60. However, the key role of TGase 2 in RCC was not clear. The down-regulation of TGase 2 was found to stabilize p53 expression, thereby inducing a 3- to 10-fold increase in apoptosis for 786-O, A498, CAKI-1, and ACHN cell lines by DAPI staining. MEF cells from TGase 2-/- mice showed stabilized p53 under apoptotic stress to compare to MEFs from wild-type mice. TGase 2 directly cross links the DNA binding domain of p53, leading to p53 depletion via autophagy in RCC. TGase 2 and p53 expression showed an inverse relationship in RCC cells. This finding implies that induced expression of TGase 2 promotes tumor cell survival through p53 depletion in RCC.-Ku, B.M., Kim, D.-S. Kim, K.-H., Yoo, B.C., Kim, S.-H., Gong, Y.-D., Kim, S.-Y. Transglutaminase 2 inhibition found to induce p53 mediated apoptosis in renal cell carcinoma.
AB - Renal cell carcinoma (RCC), the predominant form of kidney cancer, is characterized by high resistance to radiation and chemotherapy. This study shows that expression of protein cross-linking enzyme transglutaminase 2 (TGase 2) is markedly increased in 7 renal cell carcinoma (RCC) cell lines in comparison to HEK293 and other cancer cell lines, such as NCI 60. However, the key role of TGase 2 in RCC was not clear. The down-regulation of TGase 2 was found to stabilize p53 expression, thereby inducing a 3- to 10-fold increase in apoptosis for 786-O, A498, CAKI-1, and ACHN cell lines by DAPI staining. MEF cells from TGase 2-/- mice showed stabilized p53 under apoptotic stress to compare to MEFs from wild-type mice. TGase 2 directly cross links the DNA binding domain of p53, leading to p53 depletion via autophagy in RCC. TGase 2 and p53 expression showed an inverse relationship in RCC cells. This finding implies that induced expression of TGase 2 promotes tumor cell survival through p53 depletion in RCC.-Ku, B.M., Kim, D.-S. Kim, K.-H., Yoo, B.C., Kim, S.-H., Gong, Y.-D., Kim, S.-Y. Transglutaminase 2 inhibition found to induce p53 mediated apoptosis in renal cell carcinoma.
KW - Autophagy
KW - Kidney cancer
KW - Protein cross-linking
UR - http://www.scopus.com/inward/record.url?scp=84883328678&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883328678&partnerID=8YFLogxK
U2 - 10.1096/fj.12-224220
DO - 10.1096/fj.12-224220
M3 - Article
C2 - 23704086
AN - SCOPUS:84883328678
SN - 0892-6638
VL - 27
SP - 3487
EP - 3495
JO - FASEB Journal
JF - FASEB Journal
IS - 9
ER -