The role of the CDP-choline pathway in the anoikis resitance of Ras transformed intestinal epithelial cells

Abstract

Phosphatidylcholine (PC) is an essential component of biological membranes and is synthesized by the CDP-choline pathway under the control of the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase-alpha (CCT?). Ras transformed cells have increased lipid synthesis; the aim of this study was to determine if upregulation of CCT? was part of this transformed phenotype. Rat intestinal epithelial cell lines (IEC) and three oncogenic H-ras expressing IEC (IEC-Ras) were used to investigate the role of CCT? and phosphatidylcholine (PC) synthesis in resistance to detachment dependant apoptosis, termed anoikis. IEC-Ras have increased CCT? expression within the nucleus. Reduction of CCT? expression with lentiviral short hairpin RNA sensitized IEC-Ras to anoikis and decreased PC degradation, but did not change PC synthesis. Thus, in addition to CCT? being involved in anoikis-resistance in IEC-Ras these data indicate the possibility that it may also have nuclear-specific functions.