Isolation and characterization of novel RECK tumor suppressor gene splice variants

Autor(es):Mostrar menos -

Trombetta-Lima, Marina ^{[1, 2]} ; Brochado Winnischofer, Sheila Maria ^[3] ; Almeida Demasi, Marcos Angelo ^{[1, 2]} ; Astorino Filho, Renato ^{[1, 2]} ; Oliveira Carreira, Ana Claudia ^{[1, 2]} ; Wei, Beiyang ^[4] ; Ribas, Thais de Assis ^[2] ; Konig, Michelle Silberspitz ^[2] ; Bowman-Colin, Christian ^{[2, 5]} ; Oba-Shinjo, Sueli Mieko ^{[2, 6]} ; Nagahashi Marie, Suely Kazue ^{[2, 6]} ; Stetler-Stevenson, William ^[4] ; Sogayar, Mari Cleide ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, NUCEL NETCEM Fac Med, BR-05360120 Sao Paulo, SP - Brazil

^[3] Univ Fed Parana, Dept Bioquim & Biol Mol, BR-81531990 Curitiba, Parana - Brazil

^[4] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 - USA

^[5] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 - USA

^[6] Univ Sao Paulo, Fac Med, Dept Neurol, BR-01246000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ONCOTARGET; v. 6, n. 32, p. 33120-33133, OCT 20 2015.
• Citações Web of Science: 8

Resumo

Glioblastoma multiforme is the most common and lethal of the central nervous system glial-derived tumors. RECK suppresses tumor invasion by negatively regulating at least three members of the matrix metalloproteinase family: MMP-9, MMP-2, and MT1-MMP. A positive correlation has been observed between the abundance of RECK expression in tumor samples and a more favorable prognosis for patients with several types of tumors. In the present study, novel alternatively spliced variants of the RECK gene: RECK-B and RECK-I were isolated by RT-PCR and sequenced. The expression levels and profiles of these alternative RECK transcripts, as well as canonical RECK were determined in tissue samples of malignant astrocytomas of different grades and in a normal tissue RNA panel by qRT-PCR. Our results show that higher canonical RECK expression, accompanied by a higher canonical to alternative transcript expression ratio, positively correlates with higher overall survival rate after chemotherapeutic treatment of GBM patients. U87MG and T98G cells over-expressing the RECK-B alternative variant display higher anchorage-independent clonal growth and do not display modulation of, respectively, MMP-2 and MMP-9 expression. Our findings suggest that RECK transcript variants might have opposite roles in GBM biology and the ratio of their expression levels may be informative for the prognostic outcome of GBM patients. (AU)

• Processo FAPESP: 08/53971-5 - Análise do papel do gene supressor de tumor RECK na regulação do ciclo celular e caracterização de sua isoforma alternativa
• Beneficiário: Marina Trombetta Lima
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 10/51634-1 - Mapeamento de nichos neurogênicos no lobo temporal humano
• Beneficiário: Mari Cleide Sogayar
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 04/12133-6 - Procura de marcadores moleculares relacionados ao diagnóstico e prognóstico de tumores do sistema nervoso central
• Beneficiário: Suely Kazue Nagahashi Marie
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 01/10707-7 - Bases moleculares do controle da proliferação celular e origem de neoplasias na era de genômica e proteômica
• Beneficiário: Mari Cleide Sogayar
• Modalidade de apoio: Auxílio à Pesquisa - Temático