Fra-1 and c-Fos Activates Phospholipid Synthesis to Support Growth of Breast Tumors

CASTRO GM; MOTRICH RD; CAPUTTO BL

San Miguel de Tucuman

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2009

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Up to date, no other inducible proteins have been found capable of replacing c-Fos in its capacity to activate phospholipid synthesis for membrane biogenesis. However, an in-silico search revealed that Fra-1 has a BD (Basic Domain) practically identical to c-Fos, varying in a single basic aminoacid. Consequently, the capacity of Fra-1 to activate phospholipid synthesis was examined in NIH and T98G cells and found to be similar to that of c-Fos. As Fra-1 expression pattern does not overlap with that of c-Fos during normal cell growth, we studied its putative role in breast cancer cell growth, a situation in which Fra-1 over expression has been reported. Confocal microscopy analysis showed Fra-1 co-localizing with the endoplasmic reticulum (ER) marker calnexin, in growing MDA-MB231 and MCF7 cells. In addition, cellular fractioning assays revealed that stripping membranes of associated proteins (0.1 M KCl) results in quiescent cell phospholipid synthesisrates which were restored to initial activated rates upon addition of recombinant Fra-1 to these stripped membranes demonstrating that Fra-1 is able per se of activating lipid synthesis. Finally, over expression of Fra-1 was shown in human breast tumor samples as compared to normal tissue which co-localized with ER markers. Our results indicated that c-Fos and/or Fra-1 support breast tumor growth by activating phospholipid synthesis.