These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Dominant-negative transcription factor AP-2 augments SB-2 melanoma tumor growth in vivo.
    Author: Gershenwald JE, Sumner W, Calderone T, Wang Z, Huang S, Bar-Eli M.
    Journal: Oncogene; 2001 Jun 07; 20(26):3363-75. PubMed ID: 11423987.
    Abstract:
    We have previously demonstrated that the transition of melanoma to the metastatic phenotype is associated with a loss of expression of the transcription factor AP-2. To further investigate the role of AP-2 in the progression of human melanoma, we attempted to inactivate AP-2 in primary cutaneous SB-2 melanoma cells by using a dominant-negative AP-2, or AP-2B, gene. AP-2B is an alternatively spliced AP-2 variant capable of inhibiting AP-2 trans-activator function. Stable transfection of primary cutaneous melanoma SB-2 cells with the dominant-negative AP-2B gene was confirmed by RT--PCR and Northern blot analyses. Electromobility shift assay using nuclear extracts from these cell lines demonstrated decreased functional binding of AP-2B-transfected cells to the AP-2 consensus binding sequence compared with neo-transfected controls. In addition, CAT activity driven by a construct containing the AP-2 consensus binding sequence was downregulated in the AP-2B transfected cells, indicating AP-2 activity was quenched in the transfected cells. Orthotopic (subcutaneous) injection of the dominant-negative (AP-2B)-transfected cell lines into nude mice increased their tumorigenicity compared to control neo-transfected cells. The AP-2B-transfected cells displayed an increase in MMP-2 expression (by Northern blot) and MMP-2 activity (by zymography), which resulted in an increase in invasiveness through Matrigel-coated filters. The AP-2B-transfected tumors also displayed an increase in MMP-2 expression, microvessel density, and angiogenesis in vivo. These results demonstrate that inactivation of AP-2 contributes to the progression of melanoma, at least partially via deregulation of the MMP-2 gene.
    [Abstract] [Full Text] [Related] [New Search]