title: MHC class I-related chain A and B ligands are differentially expressed in human cervical cancer cell lines.
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.
authors.affiliation: Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Susana
authors.initials: S
authors.lastname: Del Toro-Arreola
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
authors.forename: Naela
authors.initials: N
authors.lastname: Arreygue-Garcia
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
authors.forename: Adriana
authors.initials: A
authors.lastname: Aguilar-Lemarroy
authors.affiliation: Translational Immunology Unit, German Cancer Research Center (DKFZ) Im Neuenheimer Feld 280 69120-Heidelberg, Germany.
authors.forename: Angel
authors.initials: A
authors.lastname: Cid-Arregui
authors.affiliation: Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Miriam
authors.initials: M
authors.lastname: Jimenez-Perez
authors.affiliation: Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.|División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
authors.forename: Jesse
authors.initials: J
authors.lastname: Haramati
authors.affiliation: División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
authors.forename: Patricio
authors.initials: P
authors.lastname: Barros-Nuñez
authors.affiliation: Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Oscar
authors.initials: O
authors.lastname: Gonzalez-Ramella
authors.affiliation: Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Alicia
authors.initials: A
authors.lastname: Del Toro-Arreola
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
authors.forename: Pablo
authors.initials: P
authors.lastname: Ortiz-Lazareno
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
authors.forename: Georgina
authors.initials: G
authors.lastname: Hernandez-Flores
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Bravo-Cuellar
authors.affiliation: Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Adrian
authors.initials: A
authors.lastname: Daneri-Navarro
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, México.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Jave-Suarez