CCT CORDOBA   20420
CENTRO CIENTIFICO TECNOLOGICO CONICET - CORDOBA
Centro Científico Tecnológico - CCT
congresos y reuniones científicas
Título:
Fra-1 and c-Fos support breast tumor growth by activating phospholipids synthesis
Autor/es:
MOTRICH, RD; CAPUTTO, BL
Lugar:
San Miguel de Tucuman
Reunión:
Congreso; XLVII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2011
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)
Resumen:
In addition to its AP-1 activity, c-Fos activates phospholipid synthesis supporting membrane biogenesis for cell growth. c-Fos basic domain (BD) is essential for this activity. Fos-related antigen 1 (Fra-1), another Fos family member, shares an almost identical BD and also exerts lipid synthesis activating capacity. We studied if Fra-1 participates in breast cancer cell growth by activating phospholipid synthesis, a situation in which its overexpression has been recently reported. Growing MDA-MB 231 and MCF7 cells overexpress Fra-1 and c-Fos which co-localize with calnexin, an endoplasmic reticulum marker. Stripping membranes of associated proteins (1 M KCl treatment), results in quiescent cell phospholipid synthesis rates which are restored to initial activated values upon addition of recombinant Fra-1 or c-Fos to the assays. Similar results were verified in human breast tumor samples: phospholipid synthesis was significantly higher in tumors as compared to normal tissue but it was significantly reduced when subjecting tumor samples to 1M KCl treatment, whereas the addition of recombinant Fra-1 or c-Fos restored phospholipid synthesis to initial rates. Moreover, both phospholipid synthesis and cell proliferation were abrogated by neutralizing Fra-1 and/or c-Fos activity. Our results indicate that both Fra-1 and c-Fos support breast tumor growth by activating phospholipid synthesis.