Acetaminophen and Estradiol Differentially Alter the Expression of Estrogen-Responsive Genes in Human Breast Cancer Cells

Details

• Personal Author:
  Gadd S ; Miller MR
• Description:
  Studies from this lab have reported that acetaminophen stimulates proliferation of estrogen-responsive (E2-responsive) MCF-7 breast cancer cells, but does not stimulate proliferation of E2-nonresponsive MDA-MB-231 breast cancer cells. Furthermore, acetaminophen-induced breast cancer cell proliferation is inhibited by anti estrogens, indicating acetaminophen alters breast cancer cell proliferation by an estrogen receptor (ER)-mediated pathway. However, ER binding assays demonstrate that acetaminophen does not compete with E2 for ER binding. It is possible that acetaminophen activates the ER as a transcription factor via an alternative pathway. This study tested the hypothesis that acetaminophen activates the ER as a transcription factor by a mechanism other than directly binding ER. Ribonuclease protection assays were used to establish the effects of E2 and acetaminophen on expression of various genes in E2-responsive (MCF-7) and nonresponsive (MDAMB-231) breast cancer cells. In MCF-7 cells, E2 significantly induced the level of c-myc, bcl-2, c-fos, bax and GADD45 RNAs, but acetaminophen only induced expression of c-myc RNA. Furthermore, the magnitude and time course of acetaminophen and E2 induction of c-myc expression were different: E2 induced c-myc -2fold at 1 hour, while acetaminophen induced c-myc approximately 1.45 fold at 2-4 hours. In MDA-MB-231 cells, E2 did not alter the expression of any of the genes examined, while acetaminophen treatment resulted in small, but significant, increases in bax, GADD45, and p21 expression. The finding that acetaminophen induces c-myc RNA expression in MCF-7 cells, but not in MDA-MB-231 cells, is consistent with a stimulatory effect of this drug on E2-responsive breast cancer cell proliferation. However, the different effects of acetaminophen and E2 on expression of other genes indicates ER is differentially activated by E2 and acetaminophen as a transcription factor. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Genetics Neoplasms Occupational Health Safety
• Keywords:
  Breast-cancer Cancer Cancer-rates Cell-cultures Genes Medicinal-chemicals
• ISSN:
  1096-6080
• Publisher:
  Oxford University Press
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  60
• Issue:
  1
• NIOSHTIC Number:
  nn:20025823
• Citation:
  Toxicologist 2001 Mar; 60(1):390
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:309c7e2091b3e3b2f0a974ae8b334475a02ba650c426e77fe543f29084f427ae7f8cd49ee40a5e49fe76c7b619043215d965f5ba44524017c2dbff04c3f7a6fc
• Download URL:
  https://stacks.cdc.gov/view/cdc/197039/cdc_197039_DS1.pdf
• File Type:
  [PDF - 126.19 KB ]