Over-Expression of erbB2 Enhances Ethanol-Stimulated Intracellular Signaling and Invasion of Human Mammary Epithelial and Breast Cancer Cells

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. Over-expression 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 (EGFRlErbB1), ErbB2/neu, ErbB3, and ErbB4. Particularly, ErbB2 plays a pivotal role in Erb8-mediated activities. Here we demonstrated that amplification of ErbB2 expression sensitized a cellular response to ethanol. Human breast cancer cells or mammary epithelial cells with a high expression of Erb82 exhibited an enhanced response to ethanol-stimulated cell invasion. On the other hand, ethanol-mediated cell proliferation was similar between the cells over-expressing ErbB2 and the cells with normal expression levels. In the cells over-expressing ErbB2, ethanol was more effective in the activation of JNKs and p38 MAPK as well as the induction of reactive oxygen species (ROS) than the cell with normal ErbB2 expression. Blockage of either JNKs or p38 MAPK activation eliminated ethanol-mediated cell invasion. In contrast, inhibition of hydrogen peroxide formation by catalase had little effect on ethanol-induced cell invasion. These results indicated that ethanol-induced cell invasion was mediated by JNKs and p38 MAPK, but was independent of ROS formation. Our study suggests that over-expression of ErbB2 may augment ethanol-elicited signaling and promote ethanol-stimulated tumor metastasis. [Description provided by NIOSH]
• Subjects:
  Carcinogens Ethanol Genetics Neoplasms Occupational Health Safety
• Keywords:
  Breast-cancer Cancer Carcinogenesis Cell-biology Cell-function Cellular-function Ethanols Genetic-disorders Genetic-factors Tumorigenesis Tumors

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• ISSN:
  0197-016X
• Publisher:
  American Association for Cancer Research
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• 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:
  44
• NIOSHTIC Number:
  nn:20035517
• Citation:
  Proceedings of the American Association for Cancer Research (AACR) 94th Annual Meeting, July 11-14, 2003, Washington, DC. 2nd edition. Philadelphia, PA: American Association for Cancer Research, 2003 Jul; 44:1224
• CAS Registry Number:
  Ethanol (CAS RN 64-17-5)
• Federal Fiscal Year:
  2003
• Peer Reviewed:
  False
• Source Full Name:
  Proceedings of the American Association for Cancer Research (AACR) 94th Annual Meeting, July 11-14, 2003, Washington, DC
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7f1523e0708de3220ac32d057b68259dd89967619a2449095d722813b33c3e4dc6f70b7a198fde94291404aa9ae625bbeaaf2ca2f3151b0305dce8f508c65271
• Download URL:
  https://stacks.cdc.gov/view/cdc/187349/cdc_187349_DS1.pdf
• File Type:
  [PDF - 253.36 KB ]