Role of estradiol receptor-α in differential expression of 2,3,7,8- tetrachlorodibenzo-p-dioxin-inducible genes in the RL95-2 and KLE human endometrial cancer cell lines

N. R. Jana, S. Sarkar, M. Ishizuka, J. Yonemoto, C. Tohyama, H. Sone

Research output: Contribution to journalArticlepeer-review

Abstract

The present study was conducted to investigate the mechanism of the response of human uterine endometrial carcinoma cells, RL95-2 and KLE, to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). RL95-2 cells were highly responsive to TCDD in terms of cytochrome P4501A1 (CYP1A1), cytochrome P4501B1 (CYP1B1), and plasminogen activator inhibitor-2 (PAI-2), whereas KLE cells showed little stimulatory effects only at high doses. Neither showed any growth inhibition upon exposure to TCDD. KLE cells expressed higher levels of aryl hydrocarbon receptor (AhR) than RL95-2 and gel mobility shift assay also identified more liganded AhR-ARNT complex bound to xenobiotic response elements (XRE). TCDD had no down-regulatory effects on the expression of either AhR or the estradiol receptor (ER). Though both cell types expressed ER-a almost equally, immunofluorescence demonstrated a defect in its nuclear translocation in KLE cells where ER-a was mainly cytoplasmic and estradiol-17/β (E2) was unable to translocate it to the nucleus. However, both cells were nonresponsive to E2 in terms of transcriptional activation and transient expression of normal ER-α restored the E2 responsiveness. Transient expression of ER-α in KLE cells also restored its responsiveness to TCDD on transcriptional activation. Collectively, these results indicate that ER-α acts as a positive modulator in regulation of the TCDD-inducible genes.

Original languageEnglish (US)
Pages (from-to)31-39
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume368
Issue number1
DOIs
StatePublished - Aug 1 1999

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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