Lipogenic enzymes fatty acid synthase and acetyl-coenzyme A carboxylase are coexpressed with sterol regulatory element binding protein and Ki-67 in fetal tissues

Endogenous fatty acid synthesis has been observed in some rapidly prolifera ting cells and tissues, both normal and neoplastic, and probably supports m embrane synthesis. Sterol regulatory element binding proteins (SREBPs) are transcription factors that regulate the expression of genes for both choles terol and fatty acid synthesis. The inactive precursor form resides in cyto plasmic membranes. Intracellular lipid depletion triggers proteolytic cleav age of SREBP, allowing the amino terminus to enter the nucleus and activate the expression of enzymes, including acetyl-CoA carboxylase (ACC) and fatt y acid synthase (FAS), major biosynthetic enzymes for fatty acid synthesis. The expression patterns of ACC, FAS, SREBP, and Ki-67 in fetal tissues wer e compared to determine whether SREBP is likely to participate in the regul ation of proliferation-associated fatty acid synthesis during fetal growth. Tissues from 22 fetuses, 12 first-trimester and 10 second-trimester (range 7.0 to 21.6 weeks), were studied. Serial 5-mu m sections were stained with antibodies to ACC, FAS, SREBP, and Ki-67 and were compared. ACC, FAS, SREB P, and Ki-67 were coexpressed in the proliferative compartments of the inte stines, skin, and kidney. ACC, FAS, and Ki-67 were coexpressed with little SREBP in lung and cytotrophoblast. SREBP, ACC, and FAS were coexpressed wit hout Ki-67 in hepatocytes, ganglion cells, and intermediate trophoblast. Th e close linkage of SREBP, ACC, FAS, and Ki-67 in some proliferating fetal t issues suggests that in these tissues SREBP participates in the transcripti onal regulation of lipogenic genes during proliferation. SREBP, ACC, and FA S coexpression without Ki-67 occurs in differentiated tissues that may synt hesize fatty acids for other functions.