Overexpression of ErbB2 Enhances Ethanol-Stimulated Intracellular Signaling and Invasion of Human Mammary Epithelial and Breast Cancer Cells In Vitro

Details

• Personal Author:
  Leonard, Stephen S. ; Lin H ; Luo J ; Ma C ; Shi X ; Ye J
• Description:
  Both epidemiological and experimental studies indicate that ethanol is a tumor promoter and may promote metastasis of breast cancer. However, the molecular mechanisms underlying ethanol-mediated tumor promotion remain unknown. Overexpression of ErbB proteins in breast cancer patients is generally associated with poor prognosis. The ErbB proteins are a family of receptor kinases that include four closely related members: epidermal growth factor receptor (EGFR/ErbB1), ErbB2/neu, ErbB3, and ErbB4. Particularly, ErbB2 plays a pivotal role in ErbB-mediated activities. Here we demonstrated that amplification of ErbB2 expression sensitized a specific cellular response to ethanol. Human breast cancer cells or mammary epithelial cells with a high expression of ErbB2 exhibited an enhanced response to ethanol-stimulated cell invasion in vitro. Ethanol also stimulated cell proliferation; however, this stimulation was independent of ErbB2 levels. Ethanol triggered divergent intracellular signaling among cells expressing different ErbB2 levels. In the cells overexpressing ErbB2, ethanol was more effective in the activation of c-Jun NH2 terminal protein kinases (JNKs) and p38 mitogen-activated protein kinase (p38 MAPK) as well as the induction of reactive oxygen species (ROS) than the cells with normal ErbB2 expression. Blockage of either JNKs or p38 MAPK activation eliminated ethanol-mediated cell invasion. In contrast, the reduction of hydrogen peroxide concentration by catalase exposure had little effect on ethanol-induced cell invasion. These results indicated that ethanol-induced cell invasion was primarily mediated by JNKs and p38 MAPK, whereas the involvement of ROS formation might be minimal. Our study suggests that overexpression of ErbB2 may augment ethanol-elicited signaling and promote ethanol-stimulated tumor metastasis. [Description provided by NIOSH]
• Subjects:
  Epidemiology Ethanol Growth Neoplasms Occupational Health Safety
• Keywords:
  Author Keywords: Alcohol Breast Cancer Cancer Cellular Reactions Ethanols Growth Factors In Vitro Studies Metastasis Proteins Reactive Oxygen Species Signal Transduction Tumors

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• ISSN:
  0950-9232
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Louisiana ; OSHA Region 3 ; OSHA Region 6 ; 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:
  22
• Issue:
  34
• NIOSHTIC Number:
  nn:20023517
• Citation:
  Oncogene 2003 Aug; 22(34):5281-5290
• Email:
  jluo@hsc.wvu.edu
• CAS Registry Number:
  Ethanol (CAS RN 64-17-5) ; Hydrogen peroxide (CAS RN 7722-84-1)
• Federal Fiscal Year:
  2003
• Peer Reviewed:
  True
• Source Full Name:
  Oncogene
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e11a12e170fffd3d5dabf3a8237580b1b8e05e361af0c99d668289743629c7dfff0a8e7fba9b24b83b73031031257ca01805da02ab6f8fd7754d9f98bf111267
• Download URL:
  https://stacks.cdc.gov/view/cdc/195892/cdc_195892_DS1.pdf
• File Type:
  [PDF - 486.47 KB ]