Investigation of HLA class I downregulation in breast cancer by RT-PCR

Giulio Lelio Palmisano, Maria Pia Pistillo, Paolo Capanni, Cinzia Pera, Guido Nicolò, Sandra Salvi, Luisa Perdelli, Gennaro Pasciucco, Giovanni Battista Ferrara

Research output: Contribution to journalArticlepeer-review

Abstract

Downregulation of HLA class I antigen expression has been reported in a significant proportion of primary breast carcinomas suggesting an escape mechanism from CTL mediated lysis leading to tumor dissemination and metastasis: We have previously reported the biochemical and immunohistochemical analysis of HLA total class I (W6/32 mAb), α-chain (Q1/28,TP25.99 mAbs) and β2-microglobulin (Namb-1 mAb) subunits expression in 25 primary breast carcinomas. This study at protein level resulted in the observation of three different HLA class I expression patterns by both techniques: high, low, and absent downregulation patterns. To better characterize the HLA class I antigens downregulation we extended such analysis also at RNA level by RT-PCR using HLA-A, HLA-B, HLA-C, and β2-microglobulin specific primers either in breast cancer or normal tissues derived from the same patient. None (100%) of the α-chain genes analyzed in patient tumor tissues showed significant reduction of expression. In 10 patients out of 25 (40%) the β2-microglobulin gene showed complete loss of expression compared with the corresponding normal tissue counterpart, which showed a constitutive expression, whereas in 2 patients (12.5%) its expression was comparable with the normal counterpart. Sequence analysis at genomic level revealed no defects affecting β2-microglobulin gene in those patients showing lack of expression. Also TAP1 and TAP2 genes expression were investigated in order to confirm or exclude involvement of the MHC class I molecules assembling machinery. The RT-PCR approach mainly confirmed our β2-microglobulin biochemical analysis indicating that in breast cancer specimens it is possible to address the HLA class I gene downregulation as a phenomenon occurring at post-transcriptional level mainly affecting the β2-microglobulin gene expression.

Original languageEnglish
Pages (from-to)133-139
Number of pages7
JournalHuman Immunology
Volume62
Issue number2
DOIs
Publication statusPublished - 2001

Keywords

  • β-microglobulin
  • Breast cancer
  • HLA class I downregulation
  • RT-PCR
  • TAP genes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Fingerprint

Dive into the research topics of 'Investigation of HLA class I downregulation in breast cancer by RT-PCR'. Together they form a unique fingerprint.

Cite this