Transglutaminase 2 inhibition found to induce p53 mediated apoptosis in renal cell carcinoma.

Abstract

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.

• Authors: Bo Mi Ku, Dae-Seok Kim, Kyung-Hee Kim, Byong Chul Yoo, Seok-Hyun Kim, Young-Dae Gong, Soo-Youl Kim
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 27 Issue 9 Pg. 3487-95 (Sep 2013) ISSN: 1530-6860 [Electronic] United States
• PMID: 23704086 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• Tumor Suppressor Protein p53
• Protein Glutamine gamma Glutamyltransferase 2
• Transglutaminases
• GTP-Binding Proteins

Topics

• Animals
• Apoptosis (genetics, physiology)
• Blotting, Western
• Carcinoma, Renal Cell (enzymology, genetics, metabolism)
• Cell Line
• Cell Line, Tumor
• Electrophoretic Mobility Shift Assay
• Fluorescent Antibody Technique
• GTP-Binding Proteins (genetics, metabolism)
• Humans
• Immunoprecipitation
• Mice
• Mice, Knockout
• Protein Glutamine gamma Glutamyltransferase 2
• RNA, Small Interfering (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Transglutaminases (genetics, metabolism)
• Tumor Suppressor Protein p53 (genetics, metabolism)