Sp1 and Sp3 transcription factors upregulate the proximal promoter of the human prostate-specific antigen gene in prostate cancer cells

Toshitaka Shin; Hideaki Sumiyoshi; Noritaka Matsuo; Fuminori Satoh; Yoshio Nomura; Hiromitsu Mimata; Hidekatsu Yoshioka

doi:10.1016/j.abb.2005.01.002

Sp1 and Sp3 transcription factors upregulate the proximal promoter of the human prostate-specific antigen gene in prostate cancer cells

Arch Biochem Biophys. 2005 Mar 15;435(2):291-302. doi: 10.1016/j.abb.2005.01.002.

Authors

Toshitaka Shin¹, Hideaki Sumiyoshi, Noritaka Matsuo, Fuminori Satoh, Yoshio Nomura, Hiromitsu Mimata, Hidekatsu Yoshioka

Affiliation

¹ Department of Anatomy, Biology, and Medicine, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan. shintosh@med.oita-u.ac.jp

PMID: 15708372
DOI: 10.1016/j.abb.2005.01.002

Abstract

The serum level of prostate-specific antigen (PSA) is useful as a clinical marker for diagnosis and assessment of the progression of prostate cancer, and in evaluating the effectiveness of treatment. We characterized four Sp1/Sp3 binding sites in the proximal promoter of the PSA gene. In a luciferase assay, these sites contributed to the basal promoter activity in prostate cancer cells. In an electrophoretic mobility shift assay and chromatin immunoprecipitation assay, we confirmed that Sp1 and Sp3 bind to these sites. Overexpression of wild-type Sp1 and Sp3 further upregulated the promoter activity, whereas overexpression of the Sp1 dominant-negative form or addition of mithramycin A significantly reduced the promoter activity and the endogenous mRNA level of PSA. Among the four binding sites, a GC box located at nucleotides -53 to -48 was especially critical for basal promoter activity. These results indicate that Sp1 and Sp3 are involved in the basal expression of PSA in prostate cancer cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites / genetics
Chromatin Immunoprecipitation
DNA Primers / genetics
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Electrophoretic Mobility Shift Assay
Gene Expression Regulation, Neoplastic / drug effects
Gene Expression Regulation, Neoplastic / genetics
Genes, Reporter / genetics
Humans
Male
Plicamycin / analogs & derivatives*
Plicamycin / pharmacology
Promoter Regions, Genetic*
Prostate-Specific Antigen / genetics*
Prostate-Specific Antigen / metabolism
Prostatic Neoplasms / genetics*
Prostatic Neoplasms / metabolism
RNA, Messenger / genetics
Sp1 Transcription Factor / genetics*
Sp1 Transcription Factor / metabolism
Sp3 Transcription Factor
Transcription Factors / genetics*
Transcription Factors / metabolism
Tumor Cells, Cultured

Substances

DNA Primers
DNA-Binding Proteins
RNA, Messenger
SP3 protein, human
Sp1 Transcription Factor
Transcription Factors
Sp3 Transcription Factor
mithramycin A
Prostate-Specific Antigen
Plicamycin