MECHANISMS OF DEREGULATED HER2/NEU EXPRESSION IN BREAST-CANCER CELL-LINES

  • Authors:
    • SJ MILLER
    • TC SUEN
    • TB SEXTON
    • MC HUNG
  • View Affiliations

  • Published online on: March 1, 1994     https://doi.org/10.3892/ijo.4.3.599
  • Pages: 599-608
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Abstract

Mechanisms that result in HER2/neu over-expression in breast cancer were examined by studying breast cancer cell lines that express much higher levels of HER2/neu mRNA than normal breast tissue while maintaining a near normal HER2/neu gene copy number. Nuclear run-on experiments indicate that the breast cancer cell lines MDA-MB453, BT483 and BT474 have an increased HER2/neu gene transcription rate. By using HER2/neu promoter-CAT constructs, we show that the enhanced HER2/neu transcription rate in MDA-MB453 is due to activation of the gene in trans. We have localized a 13-bp element on the gene promoter that is required for the increased transcription rate and have demonstrated sequence specific interaction of this fragment with a nuclear protein complex. We have also shown that in BT474 cells, transcriptional upregulation is mainly due to gene amplification and does not fully account for the levels of HER2/neu mRNA, demonstrating that deregulation of HER2/neu expression at the post-transcriptional level significantly contributes to HER2/neu overexpression in BT474 cells. Our results suggest that multiple activations of the HER2/neu gene are involved in HER2/neu over-expression in breast cancer lines and that multiple mechanisms may function simultaneously within a single cell line.

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March 1994
Volume 4 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
MILLER S, SUEN T, SEXTON T and HUNG M: MECHANISMS OF DEREGULATED HER2/NEU EXPRESSION IN BREAST-CANCER CELL-LINES. Int J Oncol 4: 599-608, 1994
APA
MILLER, S., SUEN, T., SEXTON, T., & HUNG, M. (1994). MECHANISMS OF DEREGULATED HER2/NEU EXPRESSION IN BREAST-CANCER CELL-LINES. International Journal of Oncology, 4, 599-608. https://doi.org/10.3892/ijo.4.3.599
MLA
MILLER, S., SUEN, T., SEXTON, T., HUNG, M."MECHANISMS OF DEREGULATED HER2/NEU EXPRESSION IN BREAST-CANCER CELL-LINES". International Journal of Oncology 4.3 (1994): 599-608.
Chicago
MILLER, S., SUEN, T., SEXTON, T., HUNG, M."MECHANISMS OF DEREGULATED HER2/NEU EXPRESSION IN BREAST-CANCER CELL-LINES". International Journal of Oncology 4, no. 3 (1994): 599-608. https://doi.org/10.3892/ijo.4.3.599