A HLA class I cis-regulatory element whose activity can be modulated by hormones

Int J Cancer. 1994 Dec 1;59(5):646-56. doi: 10.1002/ijc.2910590512.


To elucidate the basis of the down-regulation in major histocompatibility complex (MHC) class I gene expression and to identify possible DNA-binding regulatory elements that have the potential to interact with class I MHC genes, we have studied the transcriptional regulation of class I HLA genes in human breast carcinoma cells. A 9 base pair (bp) negative cis-regulatory element (NRE) has been identified using band-shift assays employing DNA sequences derived from the 5'-flanking region of HLA class I genes. This 9-bp element, GTCATGGCG, located within exon I of the HLA class I gene, can potently inhibit the expression of a heterologous thymidine kinase (TK) gene promoter and the HLA enhancer element. Furthermore, this regulatory element can exert its suppressive function in either the sense or anti-sense orientation. More interestingly, NRE can suppress dexamethasone-mediated gene activation in the context of the reported glucocorticoid-responsive element (GRE) in MCF-7 cells but has no influence on the estrogen-mediated transcriptional activation of MCF-7 cells in the context of the reported estrogen-responsive element (ERE). Furthermore, the presence of such a regulatory element within the HLA class I gene whose activity can be modulated by hormones correlates well with our observation that the level of HLA class I gene expression can be down-regulated by hormones in human breast carcinoma cells. Such interactions between negative regulatory elements and specific hormone trans-activators are novel and suggest a versatile form of transcriptional control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding, Competitive
  • Blotting, Northern
  • Breast Neoplasms
  • DNA / chemistry
  • DNA / metabolism*
  • Dexamethasone / pharmacology
  • Enhancer Elements, Genetic
  • Estrogens / pharmacology
  • Gene Expression Regulation / drug effects*
  • HLA-C Antigens / genetics
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Molecular Sequence Data
  • Mutagenesis
  • Promoter Regions, Genetic
  • RNA, Messenger / metabolism
  • Regulatory Sequences, Nucleic Acid*
  • Thymidine Kinase / genetics
  • Transcriptional Activation
  • Tumor Cells, Cultured


  • Estrogens
  • HLA-C Antigens
  • HLA-C*03 antigen
  • Histocompatibility Antigens Class I
  • RNA, Messenger
  • Dexamethasone
  • DNA
  • Thymidine Kinase