Defining Regulatory Elements in the Human KAI1 (CD 82) Metastasis Suppressor Gene

Allen C. Gao, Wei Lou, Jin Tang Dong, J. Carl Barrett, David Danielpour, John Tod Isaacs

Research output: Contribution to journalArticle

Abstract

The human KAI1 metastasis suppressor gene encodes for a 267 amino acid plasma membrane glycoprotein, which has four transmembrane domains and one large and one small extracellular domain. Plasma membrane expression of KAI1 is downregulated during the progression of several cancers to a metastatic state, including prostate, lung, and pancreatic cancers. To elucidate the mechanisms for this downregulation, an understanding of its transcriptional regulation is critical. Therefore, a set of luciferase reporter gene plasmid constructs were generated containing various 5′ flanking regions to the transcription initiation site, with or without the first exon and a portion of the first intron of the KAI1 gene. These constructs were transfected into a series of normal and malignant prostate cell lines as well as fibroblasts and the resultant luciferase activities used to define the regulatory elements for expression of the KAI1 gene. Using this approach, the minimal KAI1 promoter was found to be 0.5 kb in size and contains two regions. The first region includes the 197 bp 5′ to the transcription initiation site and the second region includes the first exon and a portion of first intron (i.e., +1 to +351 bp). This combined region result in positively regulated strong, but not epithelial specific, luciferase expression. In addition to this minimal promoter element from -197 to +351 bp, there is a second regulatory element further upstream (i.e., -735 to -197 bp), which negatively regulates luciferase expression. Additional studies of Marreiros et al. (Gene 302:155, 2003) have documented that a third regulatory element even further 5′ (i.e., -922 to -846 bp) encodes an enhancer for the KAI1 gene.

Original languageEnglish (US)
Pages (from-to)256-260
Number of pages5
JournalProstate
Volume57
Issue number4
DOIs
StatePublished - Dec 1 2003

Fingerprint

Tumor Suppressor Genes
Luciferases
Transcription Initiation Site
Introns
Exons
Down-Regulation
Cell Membrane
Genes
5' Flanking Region
Membrane Glycoproteins
Pancreatic Neoplasms
Reporter Genes
Prostate
Lung Neoplasms
Prostatic Neoplasms
Plasmids
Fibroblasts
Gene Expression
Amino Acids
Cell Line

Keywords

  • KAI1
  • Metastasis suppressor
  • Promoter
  • Prostate

ASJC Scopus subject areas

  • Urology

Cite this

Defining Regulatory Elements in the Human KAI1 (CD 82) Metastasis Suppressor Gene. / Gao, Allen C.; Lou, Wei; Dong, Jin Tang; Barrett, J. Carl; Danielpour, David; Isaacs, John Tod.

In: Prostate, Vol. 57, No. 4, 01.12.2003, p. 256-260.

Research output: Contribution to journalArticle

Gao, AC, Lou, W, Dong, JT, Barrett, JC, Danielpour, D & Isaacs, JT 2003, 'Defining Regulatory Elements in the Human KAI1 (CD 82) Metastasis Suppressor Gene', Prostate, vol. 57, no. 4, pp. 256-260. https://doi.org/10.1002/pros.10309
Gao, Allen C. ; Lou, Wei ; Dong, Jin Tang ; Barrett, J. Carl ; Danielpour, David ; Isaacs, John Tod. / Defining Regulatory Elements in the Human KAI1 (CD 82) Metastasis Suppressor Gene. In: Prostate. 2003 ; Vol. 57, No. 4. pp. 256-260.
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