| Full text | |
| Author(s): |
Almeida, Luciana O.
[1]
;
Goto, Renata N.
[1]
;
Pestana, Cezar R.
[2]
;
Uyemura, Sergio A.
[1]
;
Gutkind, Silvio
[3]
;
Curti, Carlos
[2]
;
Leopoldino, Andreia M.
[1]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Dept Quim & Fis, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil
[3] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD - USA
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | FEBS Journal; v. 279, n. 24, p. 4615-4628, DEC 2012. |
| Web of Science Citations: | 12 |
| Abstract | |
Alcohol and tobacco consumption are risk factors for head and neck squamous cell carcinoma (HNSCC). Aldehyde dehydrogenase 2 (ALDH2) and glutathione Stransferase pi 1 (GSTP1) are important enzymes for cellular detoxification and low efficiencies are implicated in cancer. We assessed the potential role of SET protein overexpression, a histone acetylation modulator accumulated in HNSCC, in gene regulation and protein activity of ALDH2 and GSTP1. SET was knocked down in HN13, HN12 and Cal27, and overexpressed in HEK293 cells; ethanol and cisplatin were the chemical agents. Cells with SET overexpression (HEK293/SET, HN13 and HN12) showed lower ALDH2 and GSTP1 mRNA levels and trichostatin A increased them (real-time PCR). Ethanol upregulated GSTP1 and ALDH2 mRNAs, whereas cisplatin upregulated GSTP1 in HEK293 cells. SET-chromatin binding revealed SET interaction with ALDH2 and GSTP1 promoters, specifically via SET NAP domain; ethanol and cisplatin abolished SET binding. ALDH2 and GSTP1 efficiency was assessed by enzymatic and comet assay. A lower ALDH2 activity was associated with greater DNA damage (tail intensity) in HEK293/SET compared with HEK293 cells, whereas HN13/siSET showed ALDH2 activity higher than HN13 cells. HN13/siSET cells showed increased tail intensity. Cisplatin-induced DNA damage response showed negative relationship between SET overexpression and BRCA2 recruitment. SET downregulated repair genes ATM, BRCA1 and CHEK2 and upregulated TP53. Cisplatin-induced cell-cycle arrest occurred in G0/G1 and S in HEK293 cells, whereas HEK293/SET showed G2/M stalling. Overall, cisplatin was more cytotoxic for HN13 than HN13/siSET cells. Our data suggest a role for SET in cellular detoxification, DNA damage response and genome integrity. (AU) | |
| FAPESP's process: | 10/08328-7 - Estudos da resistência à apoptose induzida por t-butil hidroperoxido no câncer, modelo cabeça/pescoço: vias de sinalização com ênfase na PIP3-Akt/SET, estresse oxidativo, mitocôndria e correlações |
| Grantee: | Cezar Rangel Pestana |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 10/20536-4 - Study of functions of the acidic domain and NAP domain of SET protein in cell line |
| Grantee: | Renata Nishida Goto |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 09/52228-0 - Studies on resistance to apoptosis in cancer, head/neck model: signaling via with emphasis on PIP3-Akt/SET, oxidative stress, mitochondria and relationships |
| Grantee: | Carlos Curti |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 09/10783-7 - Molecular study of hnRNP K and SET proteins on transcription and translational proteins associated in oral tumorigenesis |
| Grantee: | Luciana Oliveira de Almeida |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 10/20384-0 - Identification of genes, miRNAs and proteins regulated by set oncoprotein and associated on malignization and tumor progression in HNSCC using in vitro and in vivo models |
| Grantee: | Andréia Machado Leopoldino |
| Support Opportunities: | Regular Research Grants |