HOXB7 mRNA is overexpressed in pancreatic ductal adenocarcinomas and its knockdown induces cell cycle arrest and apoptosis

Author(s):Show less -

Chile, Thais ^[1] ; Henriques Zanella Fortes, Maria Angela ^[1] ; Cardillo Correa-Giannella, Maria Lucia ^[1] ; Brentani, Helena Paula ^[2] ; Maria, Durvanei Augusto ^[3] ; Puga, Renato David ^[4] ; de Paula, Vanessa de Jesus R. ^[2] ; Kubrusly, Marcia Saldanha ^[5] ; Novak, Estela Maria ^{[6, 7]} ; Bacchella, Telesforo ^[5] ; Giorgi, Ricardo Rodrigues ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Lab Cellular & Mol Endocrinol LIM 25, BR-01246903 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Med Sch FMUSP, Inst Psychiat, Sao Paulo - Brazil

^[3] Butantan Inst, Biochem & Biophys Lab, BR-05503900 Sao Paulo - Brazil

^[4] CIPE AC Camargo Hosp, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Sch Med, Dept Gastroenterol LIM 07 & 37, BR-01246903 Sao Paulo - Brazil

^[6] Fundacao Prosangue Hemoctr Sao Paulo, Mol Biol Lab, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Med Sch FMUSP, Pediat Clin Lab LIM 36, Sao Paulo - Brazil

• Document type: Journal article
• Source: BMC CANCER; v. 13, OCT 2 2013.
• Web of Science Citations: 26

Abstract

Background: Human homeobox genes encode nuclear proteins that act as transcription factors involved in the control of differentiation and proliferation. Currently, the role of these genes in development and tumor progression has been extensively studied. Recently, increased expression of HOXB7 homeobox gene (HOXB7) in pancreatic ductal adenocarcinomas (PDAC) was shown to correlate with an invasive phenotype, lymph node metastasis and worse survival outcomes, but no influence on cell proliferation or viability was detected. In the present study, the effects arising from the knockdown of HOXB7 in PDAC cell lines was investigated. Methods: Real time quantitative PCR (qRT-PCR) (Taqman) was employed to assess HOXB7 mRNA expression in 29 PDAC, 6 metastatic tissues, 24 peritumoral tissues and two PDAC cell lines. siRNA was used to knockdown HOXB7 mRNA in the cell lines and its consequences on apoptosis rate and cell proliferation were measured by flow cytometry and MTT assay respectively. Results: Overexpression of HOXB7 mRNA was observed in the tumoral tissues and in the cell lines MIA PaCa-2 and Capan-1. HOXB7 knockdown elicited (1) an increase in the expression of the pro-apoptotic proteins BAX and BAD in both cell lines; (2) a decrease in the expression of the anti-apoptotic protein BCL-2 and in cyclin D1 and an increase in the number of apoptotic cells in the MIA PaCa-2 cell line; (3) accumulation of cell in sub-G1 phase in both cell lines; (4) the modulation of several biological processes, especially in MIA PaCa-2, such as proteasomal ubiquit-independent catabolic process and cell cycle. Conclusion: The present study confirms the overexpression of HOXB7 mRNA expression in PDAC and demonstrates that decreasing its protein level by siRNA could significantly increase apoptosis and modulate several biological processes. HOXB7 might be a promising target for future therapies. (AU)

• FAPESP's process: 10/01421-1 - Functional analysis, expression and mutation of homeobox gene (HOXB7) in pancreatic adenocarcinomas
• Grantee: Ricardo Rodrigues Giorgi
• Support Opportunities: Regular Research Grants