ABCMdb

PMID: 22981231

Smith B, Land H
Anticancer Activity of the Cholesterol Exporter ABCA1 Gene.
Cell Rep. 2012 Sep 27;2(3):580-90. doi: 10.1016/j.celrep.2012.08.011. Epub 2012 Sep 13., [PubMed]

Sentences

No. Mutations Sentence Comment

124 ABCA1 p.Gln597Arg ABCA1 p.Cys1477Arg To this end, we utilized two missense mutations of human ABCA1 proteins (Q597R and C1477R) linked to TD and familial hypoalphalipoproteinemia (FHA), which were previously characterized to have diminished cholesterol efflux activity (Singaraja et al., 2006). Login to comment 141 ABCA1 p.Ala1407Thr ABCA1 p.Glu210Asp ABCA1 p.Ala2109Thr ABCA1 p.Asp917Tyr Two of the mutants (A1407T and A2109T) demonstrated a marked reduction in both cholesterol efflux and antitumor activity, while the other two mutants (E210D and D917Y) showed activity indistinguishable from the wild-type (wt) ABCA1 cDNA in both assays and in both human cancer cell lines used (Figure 4). Login to comment 142 ABCA1 p.Ala1407Thr ABCA1 p.Ala2109Thr Our data thus identify ABCA1 human colon cancer mutations A1407T and A2109T as loss-of-function mutations disabling both cholesterol efflux and antitumor activity. Login to comment 144 ABCA1 p.Ala1407Thr ABCA1 p.Ala2109Thr While expression of wt ABCA1 is strongly reduced following transplantation (see also Figure S1A for murine Abca1), expression of loss-of-function ABCA1 mutants A1407T and A2109T remains relatively unchanged, presumably because their antitumor activity is strongly diminished (Figure S4). Login to comment