Uteroglobin reverts the transformed phenotype in the endometrial adenocarcinoma cell line HEC-1A by disrupting the metabolic pathways generating platelet-activating factor

Uteroglobin, originally named blastokinin, is a protein synthesized and sec reted by most epithelia, including the endometrium. Uteroglobin has strong anti-inflammatory properties that appear to be due, at least in part, to it s inhibitory effect on the activity of the enzyme phospholipase A(2). In ad dition, recent experimental evidence indicates that uteroglobin exerts anti proliferative and antimetastatic effects in different cancer cells via a me mbrane receptor. The human endometrial adenocarcinoma cell line HEC-1A does not express uteroglobin. Thus, we transfected HEC-1A cells with human uter oglobin cDNA, The transfectants showed a markedly reduced proliferative pot ential as assessed by impaired plating efficiency as well as by reduced gro wth in soft agar. Cytofluorimetric analysis clearly indicated that in utero globin-transfected cells the time for completion of the cell cycle was incr eased. We previously demonstrated that HEC-1A cells actively synthesize pla telet-activating factor, one of the products of phospholipase A(2) activity . In addition, we demonstrated that platelet-activating factor stimulates t he proliferation of these cells through an autocrine loop. In uteroglobin t ransfectants, the activity of phospholipase A(2) and platelet-activating fa ctor acetyl-transferase, which are involved in the synthesis of platelet-ac tivating factor, was significantly reduced compared with wild-type and vect or-transfected cells (p < 0.05). Our results indicate that enforced express ion of uteroglobin in HEC-1A cells markedly reduced their growth potential and significantly impaired the synthesis of platelet-activating factor, an autocrine growth factor for these cells. These data suggest that one possib le mechanism for the recently observed antineoplastic properties of uterogl obin may be the inhibition of the synthesis of platelet-activating factor. Int. (C) 2000 Wiley-Liss, Inc.