Increased Gene Copy Number of the Transcription Factor E2F1 in Malignant Melanoma

Details

• Personal Author:
  Averill J ; Beas A ; Feng Y ; Goulet AC ; Honchak B ; Jefferson AM ; Johnson RC ; Lowry DT ; Nelson MA ; Rao UN ; Reynolds SH ; Sargent LM ; Senft JR
• Description:
  Translocations and unique chromosome break points in melanoma will aid in the identification of the genes that are important in the neoplastic process. We have previously shown a unique translocation in malignant melanoma cells der(12)t(12;20). The transcription factor E2F1 maps to 20q11. Increased expression of E2F has been associated with the autonomous growth of melanoma cells, however, the molecular basis has not yet been elucidated. To this end, we investigated E2F1 gene copy number and structure in human melanoma cell lines and metastatic melanoma cases. Fluorescent in situ hybridization (FISH) analysis using a specific E2F1 probe indicated increased E2F1 gene copies in melanoma cell lines compared to normal melanocytes. We also observed increased copies of the E2F1 gene in lymph node metastases of melanoma. In addition, Western blot analysis demonstrated increased E2F1 protein levels in 8 out of 9 melanoma cell lines relative to normal melanocytes. Inhibition of E2F1 expression with RNAi also reduced melanoma cell growth. Our results suggest that the release of E2F activity by elevated E2F1 gene copy numbers may play a functional role in melanoma growth. [Description provided by NIOSH]
• Subjects:
  Cells, Cultured Genetics Neoplasms Occupational Health Safety
• Keywords:
  Cancer Cell-biology Cell-cultures Cell-growth Genes Malignancy Malignant-neoplasms
• ISSN:
  1538-4047
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Arizona ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  407-412
• Volume:
  5
• Issue:
  4
• NIOSHTIC Number:
  nn:20030618
• Citation:
  Cancer Biol Ther 2006 Apr; 5(4):407-412
• Email:
  mnelson@azcc.arizona.edu
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Cancer Biology and Therapy
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:846718bd03d2ba8136f69a32ae69d94098f4952a3a799bcb38f247854ec630ce17f1b1ec8bee17eeb158916a8208b2fd18d8d515e061cb9e31863619731be2ec
• Download URL:
  https://stacks.cdc.gov/view/cdc/191165/cdc_191165_DS1.pdf
• File Type:
  [PDF - 564.12 KB ]