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MHC class I-related chain A and B ligands are differentially expressed in human cervical cancer cell lines

Susana del Toro-Arreola1, Naela Arreygue-Garcia2, Adriana Aguilar-Lemarroy2, Angel Cid-Arregui3, Miriam Jimenez-Perez1, Jesse Haramati12, Patricio Barros-Nuñez4, Oscar Gonzalez-Ramella1, Alicia del Toro-Arreola1, Pablo Ortiz-Lazareno2, Georgina Hernandez-Flores2, Alejandro Bravo-Cuellar2, Adrian Daneri-Navarro1 and Luis F Jave-Suarez2*

  • * Corresponding author: Luis F Jave-Suarez lfjave@yahoo.com

  • † Equal contributors

Author Affiliations

1 Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México

2 División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México

3 Translational Immunology Unit, German Cancer Research Center (DKFZ) Im Neuenheimer Feld 280 69120-Heidelberg, Germany

4 División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México

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Cancer Cell International 2011, 11:15  doi:10.1186/1475-2867-11-15

Published: 1 June 2011

Abstract

Background

Natural killer (NK) cells are an important resource of the innate immune system directly involved in the spontaneous recognition and lysis of virus-infected and tumor cells. An exquisite balance of inhibitory and activating receptors tightly controls the NK cell activity. At present, one of the best-characterized activating receptors is NKG2D, which promotes the NK-mediated lysis of target cells by binding to a family of cell surface ligands encoded by the MHC class I chain-related (MIC) genes, among others. The goal of this study was to describe the expression pattern of MICA and MICB at the molecular and cellular levels in human cervical cancer cell lines infected or not with human papillomavirus, as well as in a non-tumorigenic keratinocyte cell line.

Results

Here we show that MICA and MICB exhibit differential expression patterns among HPV-infected (SiHa and HeLa) and non-infected cell lines (C33-A, a tumor cell line, and HaCaT, an immortalized keratinocyte cell line). Cell surface expression of MICA was higher than cell surface expression of MICB in the HPV-positive cell lines; in contrast, HPV-negative cells expressed lower levels of MICA. Interestingly, the MICA levels observed in C33-A cells were overcome by significantly higher MICB expression. Also, all cell lines released higher amounts of soluble MICB than of soluble MICA into the cell culture supernatant, although this was most pronounced in C33-A cells. Additionally, Real-Time PCR analysis demonstrated that MICA was strongly upregulated after genotoxic stress.

Conclusions

This study provides evidence that even when MICA and MICB share a high degree of homology at both genomic and protein levels, differential regulation of their expression and cell surface appearance might be occurring in cervical cancer-derived cells.

Keywords:
MICA; MICB; Cervical cancer