RB--acetylCoA carboxylase essential to breast cancer cell survival

[Lani]

1: Cancer Res. 2006 May 15;66(10):5287-94. Related Articles, Links

Acetyl-CoA Carboxylase {alpha} Is Essential to Breast Cancer Cell Survival.

Chajes V, Cambot M, Moreau K, Lenoir GM, Joulin V.

Centre National de la Recherche Scientifique-FRE 2939, Institut Gustave Roussy, Villejuif, France and Centre National de la Recherche Scientifique-Unite Mixte de Recherche 5201, Faculte de Medecine Rockefeller, Lyon, France.

Activation of de novo fatty acid synthesis is a characteristic feature of cancer cells. We have recently described an interaction between acetyl-CoA carboxylase alpha (ACCalpha), a key enzyme in fatty acid synthesis, and BRCA1, which indicates a possible connection between lipid synthesis and genetic factors involved in susceptibility to breast and ovarian cancers. For this reason, we explored the role of ACCalpha in breast cancer cell survival using an RNA interference (RNAi) approach. We show that specific silencing of either the ACCalpha or the fatty acid synthase (FAS) genes in cancer cells results in a major decrease in palmitic acid synthesis. Depletion of the cellular pool of palmitic acid is associated with induction of apoptosis concomitant with the formation of reactive oxygen species (ROS) and mitochondrial impairment. Expression of a small interfering RNA (siRNA)-resistant form of ACCalpha mRNA prevented the effect of ACCalpha-RNAi but failed to prevent the effect of FAS gene silencing. Furthermore, supplementation of the culture medium with palmitate or with the antioxidant vitamin E resulted in the complete rescue of cells from both ACCalpha and FAS siRNA-induced apoptosis. Finally, human mammary epithelial cells are resistant to RNAi against either ACCalpha or FAS. These data confirm the importance of lipogenesis in cancer cell survival and indicate that this pathway represents a key target for antineoplastic therapy that, however, might require specific dietary recommendation for full efficacy. (Cancer Res 2006; 66(10): 5287-94).

PMID: 16707454 [PubMed - in process]

[R.B.]

Thank you very much for posting this.

Another bit for the jigsaw, and some new branches to peer down in my inexpert way.

The implication of a recognition that diet may have a part to play gives me hope that one day they will seriously trial the fats issues based on geneexpression/ outcome/ fat biopsy to determine what outcomes are possible with simple dietary prevention.

Thank you again

RB