Isolation and characterization of novel RECK tumor suppressor gene splice variants

Author(s):Show less -

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]}

Affiliation

^[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

• Document type: Journal article
• Source: ONCOTARGET; v. 6, n. 32, p. 33120-33133, OCT 20 2015.
• Web of Science Citations: 8

Abstract

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)

• FAPESP's process: 04/12133-6 - Search for molecular markers related to the diagnosis and prognosis of tumors of the central nervous system
• Grantee: Suely Kazue Nagahashi Marie
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 01/10707-7 - Molecular bases of the control of cell proliferation and origin of neoplasms in the genomic and proteomic era
• Grantee: Mari Cleide Sogayar
• Support Opportunities: Research Projects - Thematic Grants