We report herein the cDNA cloning of a novel rat acyl-CoA synthetase (ACS) that preferentially uses arachidonate and eicosapentaenoate. This newly identified ACS (designated ACS4) contains 670 amino acids and is 68% identical to rat ACS3, a previously characterized ACS that is highly expressed in brain. ACS4 was overproduced in Escherichia coli and the resulting enzyme was purified to homogeneity. The purified enzyme utilizes arachidonate and eicosapentaenoate most preferentially among C 8 -C 22 saturated fatty acids and C 14 -C 22 unsaturated fatty acids. Kinetic analyses revealed that the enzyme has a high affinity for arachidonate and eicosapentaenoate and low affinity for palmitate. ACS4 transcripts are detectable in a wide range of tissues, with the highest level in adrenal gland. Immunoreactivity to ACS4 was detected in the zona fasciculata and reticularis of adrenal gland, in the corpus luteum and stromal luteinized cells in ovary, and in the Leydig cells of testis.
A 56-year-old male treated for a gastric yolk sac tumor with an adenocarcinomatous component is described. A mixed area of reticular and glandular neoplastic components was morphologically identified in this tumor. Immunohistochemically, the yolk sac tumor expressed alpha-fetoprotein (AFP), placental alkaline phosphatase (PLAP), and cytokeratin, but was negative for carcinoembryonic antigen (CEA). The adenocarcinoma was positive for CEA and cytokeratin, partially positive for PLAP, and negative for AFP. In the mixed area, the tumor cells were positive for cytokeratin, weakly expressed AFP and PLAP, and sporadically stained for CEA both in the reticular and glandular components. This area was identified as a transitional area of the yolk sac tumor and adenocarcinoma. These findings demonstrate that the yolk sac and adenocarcinomatous components are closely related. It also suggests that the tumor arose from multipotential neoplastic mucosal epithelial cells with both yolk sac and gastric mucosal phenotypes.
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