The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation

BMC Cancer

Research Article

Laura Sichero¹  Lara Termini¹  Luisa Lina Villa²  Paula Rahal³  André Luis Giacometti Conceição³  Marília de Freitas Calmon³  Bruna Stuqui³ 

[1] Center for Translational Investigation in Oncology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 251, 8° andar, CEP 01246-000, Bairro Cerqueira César, São Paulo, Brazil;Center for Translational Investigation in Oncology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 251, 8° andar, CEP 01246-000, Bairro Cerqueira César, São Paulo, Brazil;Department of Radiology and Oncology, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Arnaldo, 251, 8° andar, CEP 01246-000, Bairro Cerqueira César, São Paulo, Brazil;Department of Biology, Instituto de Biociências, Letras e Ciências Exatas - IBILCE/UNESP, Rua Cristóvão Colombo n° 2265, Jardim Nazareth, CEP 15054-000, São José do Rio Preto, SP, Brazil;

关键词: HTRA1;    Cell proliferation;    HPV;    PDZ;   

DOI  :  10.1186/s12885-016-2873-1

 received in 2016-06-08, accepted in 2016-10-21,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundHigh-risk human papillomaviruses (HPVs) are strongly associated with the development of some malignancies. The E6 and E7 viral oncoproteins are the primary proteins responsible for cell homeostasis alteration and immortalization. Furthermore, the E6 protein from high-risk HPVs can interact with the PDZ (PSD-90/Dlg/ZO-1) domains of cellular proteins, triggering cell transformation. One protein that is associated with pathological conditions and has a PDZ domain is the protease HTRA1 (high temperature requirement 1). This protein is poorly expressed in some cancers, suggesting a tumor suppressor role. The aim of this study was to evaluate the effect of HTRA1 overexpression in HPV16-positive (CasKi) and HPV-negative (C33) cervical cell lines.MethodsThe cells were transfected with a vector containing the HTRA1 ORF or an empty vector. HTRA1 overexpression was confirmed by qRT-PCR. The cells were subjected to cell proliferation, colony formation, apoptosis and cell cycle assays.ResultsC33 cells expressing HTRA1 grew significantly fewer colonies and showed less proliferation than cells without HTRA1 expression. In contrast, in the CasKi cells overexpressing HTRA1, there was an increase in the cell growth rate and in the colonies density compared to cells expressing low levels of HTRA1. An apoptosis assay showed that HTRA1 does not interfere with the apoptosis rate in these cells. A cell cycle immunofluorescence assay revealed more CasKi cells overexpressing HTRA1 in the S phase and more C33 HTRA1-transfected cells in the G0/G1 phase, suggesting that HTRA1 plays different roles in the cell cycle progression of these cells.ConclusionsHTRA1 overexpression prevents cell proliferation in the HPV-negative cell line and increases cell proliferation in the HPV-positive cell line. Although the E6/HTRA1 interaction has already been described in the literature, more studies are required to confirm whether the present functional findings are a result of this interaction.

【 授权许可】

CC BY   
© The Author(s). 2016