Fra-1 and c-Fos support breast tumor growth by activating phospholipid synthesis

MOTRICH, RD; CAPUTTO, BL

Puerto Madryn

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2010

Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

c-Fos has been described as an activator of phospholipid synthesis in order to support membrane biogenesis during cell growth. Fra-1, a member of the c-Fos family, has a BD (Basic Domain) practically identical to c-Fos, varying in a single basic aminoacid and, in consequence, the capacity to activate phospholipid synthesis in NIH and T98G. Recently, Fra-1 overexpression has been reported in breast cancer cell growth. Taking these data into account, we studied the putative role of Fra-1 in cancer cell growth. Fra-1 was found to be overexpressed in growing MDA-MB 231 and MCF7 cells and co-localizing with the endoplasmic reticulum (ER) marker calnexin by confocal microscopy analysis. In addition, cellular fractioning assays revealed that stripping membranes of associated proteins (0,1 M KCl treatment) results in quiescent cell phospholipid synthesis rates which was restored to initial activated activated rates upon addition of recombinant Fra-1 to these stripped membranes. In parallel, Fra-1 overexpression was also found in human tumor samples as compared to normal tissue. Again, Fra-1 co-localized with ER markers and cellular fractioning assays confirmed these findings. As expected, phospholipid synthesis rates were found to be higher in tumor samples as compared to normal tissue. This elevated phospholipid synthesis was significantly reduced when subjected tumor samples to KCl treatment and replenished to initial rates by the addition of recombinant Fra-1. Our results indicated that Fra-1, as c-Fos, is able to support breast tumor growth by activating phospholipid synthesis.