Regulation of insulin-like growth factor II P3 promoter by p53: A potential mechanism for tumorigenesis

Lijuan Zhang, Fatah Kashanchi, Qimin Zhan, Shili Zhan, John N. Brady, Albert J. Fornace, Prem Seth, Lee J. Helman

Research output: Contribution to journalArticle

Abstract

Human insulin-like growth factor (IGF)-II mRNA has been shown to be expressed at high levels in a variety of tumors, including rhabdomyosarcomas. In addition, many tumors have alterations in p53 expression. To investigate whether p53 regulates IGF-II gene expression, we transfected wild-type p53 expression vectors and luciferase constructs driven by IGF-II P3 promoters into multiple cell lines. We found that p53 reduced, in a dose-dependent manner, both endogenous IGF-II P3 transcripts and transfected P3 luciferase expression. The inhibition of P3 luciferase expression by p53 was more pronounced in the two cell lines that expressed mutant p53 protein, RD, and HTB114. The element responsible for this inhibition was mapped to the minimal promoter region. We also transfected an HPV-16 E6 expression plasmid into CCL13 cells containing functional p53 and found that E6 up-regulated IGF-II P3 activity. Wild-type, but not mutant, p53 interfered with the binding of TATA-binding protein to the TATA motif of P3, although both could directly associate with human TATA-binding protein. Our results suggest that p53 may play a role in regulation of IGF-II gene expression.

Original languageEnglish (US)
Pages (from-to)1367-1373
Number of pages7
JournalCancer Research
Volume56
Issue number6
StatePublished - Mar 15 1996
Externally publishedYes

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Insulin-Like Growth Factor II
Carcinogenesis
Luciferases
TATA-Box Binding Protein
Gene Expression
Cell Line
Human papillomavirus 16
Rhabdomyosarcoma
Mutant Proteins
Genetic Promoter Regions
Neoplasms
Plasmids
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Zhang, L., Kashanchi, F., Zhan, Q., Zhan, S., Brady, J. N., Fornace, A. J., ... Helman, L. J. (1996). Regulation of insulin-like growth factor II P3 promoter by p53: A potential mechanism for tumorigenesis. Cancer Research, 56(6), 1367-1373.

Regulation of insulin-like growth factor II P3 promoter by p53 : A potential mechanism for tumorigenesis. / Zhang, Lijuan; Kashanchi, Fatah; Zhan, Qimin; Zhan, Shili; Brady, John N.; Fornace, Albert J.; Seth, Prem; Helman, Lee J.

In: Cancer Research, Vol. 56, No. 6, 15.03.1996, p. 1367-1373.

Research output: Contribution to journalArticle

Zhang, L, Kashanchi, F, Zhan, Q, Zhan, S, Brady, JN, Fornace, AJ, Seth, P & Helman, LJ 1996, 'Regulation of insulin-like growth factor II P3 promoter by p53: A potential mechanism for tumorigenesis', Cancer Research, vol. 56, no. 6, pp. 1367-1373.
Zhang L, Kashanchi F, Zhan Q, Zhan S, Brady JN, Fornace AJ et al. Regulation of insulin-like growth factor II P3 promoter by p53: A potential mechanism for tumorigenesis. Cancer Research. 1996 Mar 15;56(6):1367-1373.
Zhang, Lijuan ; Kashanchi, Fatah ; Zhan, Qimin ; Zhan, Shili ; Brady, John N. ; Fornace, Albert J. ; Seth, Prem ; Helman, Lee J. / Regulation of insulin-like growth factor II P3 promoter by p53 : A potential mechanism for tumorigenesis. In: Cancer Research. 1996 ; Vol. 56, No. 6. pp. 1367-1373.
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