| Texto completo | |
| Autor(es): |
Maciel-Silva, Paula
[1, 2]
;
Caldeira, Izabela
[1, 2]
;
Santos, Icaro de Assis
[1]
;
Oliveira Carreira, Ana Claudia
[3]
;
Siqueira, Flavia Ramos
[3]
;
Antonioli, Eliane
[4]
;
Goldberg, Anna Carla
[4]
;
Belizario, Jose Ernesto
[2]
;
Garay-Malpartida, Humberto Miguel
[1, 2]
Número total de Autores: 9
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Sch Arts Sci & Humanities, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Biomed Sci Inst, Dept Pharmacol, Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Dept Internal Med, Sch Med, Sao Paulo, SP - Brazil
[4] Hosp Israelita Albert Einstein, Sao Paulo, SP - Brazil
Número total de Afiliações: 4
|
| Tipo de documento: | Artigo Científico |
| Fonte: | BMC CANCER; v. 18, JAN 22 2018. |
| Citações Web of Science: | 3 |
| Resumo | |
Background: FAM3B/PANDER is a novel cytokine-like protein that induces apoptosis in insulin-secreting beta-cells. Since in silico data revealed that FAM3B can be expressed in prostate tumors, we evaluated the putative role of this cytokine in prostate tumor progression. Methods: FAM3B expression was analyzed by quantitative PCR in tumor tissue clinical samples and prostate tumor cell lines. Culture growth and viability of DU145 cell line were evaluated after treatment with either exogenous FAM3B protein obtained from conditioned media (CM) of 293 T cells overexpressing FAM3B or a recombinant FAM3B protein produced in a bacterial host. DU145 cells overexpressing FAM3B protein were produced by lentiviral-mediated transduction of full-length FAM3B cDNA. Cell viability and apoptosis were analyzed in DU145/FAM3B cells after treatment with several cell death inducers, such as TNF-alpha, staurosporine, etoposide, camptothecin, and serum starvation conditions. Anchorage-independent growth in soft agarose assay was used to evaluate in vitro tumorigenicity. In vivo tumorigenicity and invasiveness were evaluated by tumor xenograft growth in nude mice. Results: We observed an increase in FAM3B expression in prostate tumor samples when compared to normal tissues. DU145 cell viability and survival increased after exogenous treatment with recombinant FAM3B protein or FAM3B-secreted protein. Overexpression of FAM3B in DU145 cells promoted inhibition of DNA fragmentation and phosphatidylserine externalization in a time and dose-dependent fashion, upon apoptosis triggered by TNF-alpha. These events were accompanied by increased gene expression of anti-apoptotic Bcl-2 and Bcl-XL, decreased expression of pro-apoptotic Bax and diminished caspase-3, -8 and -9 proteolytic activities. Furthermore, inhibition of Bcl-2 antiapoptotic family proteins with small molecules antagonists decreases protective effects of FAM3B in DU145 cells. When compared to the respective controls, cells overexpressing FAM3B displayed a decreased anchorage-independent growth in vitro and increased tumor growth in xenografted nude mice. The immunohistochemistry analysis of tumor xenografts revealed a similar anti-apoptotic phenotype displayed by FAM3B-overexpressing tumor cells. Conclusions: Taken together, by activating pro-survival mechanisms FAM3B overexpression contributes to increased resistance to cell death and tumor growth in nude mice, highlighting a putative role for this cytokine in prostate cancer progression. (AU) | |
| Processo FAPESP: | 07/04513-1 - Papel da nova citocina PANDER na indução de apoptose ou proliferação celular em linhagens tumorais de próstata e de mama |
| Beneficiário: | Humberto Miguel Garay Malpartida |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |