Comparative effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on MCF-7, RL95-2, and LNCaP cells: Role of target steroid hormones in cellular responsiveness to CYP1A1 induction

Nihar Ranjan Jana, Shubhashishi Sarkar, Mayumi Ishizuka, Junzo Yonemoto, Chiharu Tohyama, Hideko Sone

Research output: Contribution to journalArticlepeer-review

Abstract

A study was conducted to investigate whether target hormones affect 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible gene expression, using as an experimental model system three human cancer cell lines, breast (MCF-7), uterine (RL95-2), and prostate (LNCaP). Exposure to TCDD induced the CYP1A1 gene in all three cell lines. MCF-7 and RL95-2 cells showed more than 15- and 10-fold induction of EROD (7-ethoxyresorufin O-deethylase) activity, respectively, compared with the less responsive LNCaP cells. Surprisingly, however, TCDD-induced reporter gene activity driven by a single XRE element was similar in RL95-2 and LNCaP cells. The steady-state levels of expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (ARNT) were similar in all three cell lines. Expression of the CYP1B1 and PAI-2 genes was induced by TCDD in MCF-7 and RL95-2, but not in LNCaP, cells. Transient coexpression of estradiol receptor-α (ER-α) with a TCDD-responsive reporter plasmid and subsequent TCDD treatment increased responsiveness to TCDD in RL95-2 and LNCaP cells. Treatment with AZA-C, a DNA methyltransferase inhibitor, enhanced responsiveness to TCDD, in terms of EROD activity in LNCaP cells, but not in MCF-7 and RL95-2 cells, suggesting that DNA methylation in the CpG dinucleotide within the XRE core sequence is another factor involved in silencing of CYP1A1 in LNCaP cells. TCDD markedly inhibited E2- or testosterone-induced reporter gene activities in all three cell lines. Conversely, these target hormones inhibited TCDD-induced EROD activity in the three cell lines. These findings suggest that TCDD and the target steroid hormones negatively regulate each other's activity.

Original languageEnglish (US)
Pages (from-to)174-180
Number of pages7
JournalMolecular Cell Biology Research Communications
Volume4
Issue number3
DOIs
StatePublished - 2000

Keywords

  • 2,3,7,8-tetrachlorodibenzo-p-dioxin
  • AhR
  • CYP1A1
  • ER
  • Human cells
  • Steroid hormone

ASJC Scopus subject areas

  • Molecular Biology

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