{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T03:41:40Z","timestamp":1768966900133,"version":"3.49.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":4144,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[1993,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Former studies have linked hepatocyte growth with liver fatty acid binding protein (L\u2010FABP) of rat liver cytosol. In search for the roles of L\u2010FABP in hepatocytes, we previously stably transfected rat L\u2010FABP sense and antisense cDNAs into rat hepatoma HTC cells that do not contain L\u2010FABP RNA or protein, thereby providing a zero\u2010background, homologous cell model of L\u2010FABP\u2010expression suitable for controlled studies of its intracellular functions in hepatocyte\u2010derived cells. The present study demonstrates the abilities of L\u2010FABP to promote DNA synthesis and cell growth, preserve cell morphology, extend survival, and act cooperatively with unsaturated fatty acids in the transfected hepatoma cells in the absence of serum. Following removal of serum, the three control L\u2010FABP\u2010nonexpressing cell lines increased in cell lines increased in cell number for 24 hr and thereafter declined, whereas the three L\u2010FABP\u2010expressing cell lines exhibited a 39% higher rate of DNA synthesis per cell at 24 hr and grew in cell number for 48 hr. As a result, at 72 hr there were 2.5\u2010fold (avg.) as many L\u2010FABP\u2010expressing cells than L\u2010FABP\u2010nonexpressing cells. In addition, the L\u2010FABP\u2010expressing cells retained their original polygonal morphology at 48 hr, when in contrast most of the control nonexpressing cells were spherical in shape with membrane blebs. In an effort to identify the agonists that collaborate with L\u2010FABP in the growth promotion and preservation of cell morphology, various free fatty acids were examined at 48 hr for their ability to elminate the differences in behavior of the two cell types in the serum\u2010free medium. The unsaturated fatty acids, oleic acid (18:1 \u03c99), linoleic acid (18:2\u03c96), \u03b1\u2010linolenic acid (18: 3\u03c93), and arachidonic acid (20:4\u03c96), at 1 \u03bcM markedly elevated the level of DNA synthesis in the more depressed control L\u2010FABP\u2010nonexpressing cells and moderately raised it in the less depressed L\u2010FABP\u2010expressing cells. In accord, the control L\u2010FABP\u2010nonexpressing cells needed 10<jats:sup>\u22126<\/jats:sup>\u201310<jats:sup>\u22125<\/jats:sup> M linoleic acid to achieve the extent of DNA synthesis attained by the expressing cells in the absence of added fatty acid. At 10 \u03bcM linoleic acid, their levels of DNA synthesis were equal. In contrast, five saturated fatty acids had no detectable effect on DNA synthesis. In addition, linoleic acid at 1 \u03bcM, but not the saturated fatty acid palmitic acid (16:0), prevented the above morphological alterations in the control L\u2010FABP\u2010nonexpressing cells observed in the absence of serum, thereby retaining their original polygonal morphology and that of the expressing cells. The findings are consistent with the concept that L\u2010FABP improves the efficacy of the utilization of unsaturated fatty acid ligands of L\u2010FABP in the formation, integrity, and fluidity of cell membranes that are involved in cell growth, morphology, and survival. \u00a9 1993 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.1041570105","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T05:35:20Z","timestamp":1109396120000},"page":"33-40","source":"Crossref","is-referenced-by-count":29,"title":["Growth promotion of transfected hepatoma cells by liver fatty acid binding protein"],"prefix":"10.1002","volume":"157","author":[{"given":"Tibor","family":"Keler","sequence":"first","affiliation":[]},{"given":"Sam","family":"Sorof","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"857","article-title":"Differential proliferative response to linoleate in cultures of epithelial cells from normal human breast and fibroadenomas","volume":"49","author":"Balakrishnan A.","year":"1989","journal-title":"Cancer Res."},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(08)61733-7"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.21.7547"},{"key":"e_1_2_1_5_1","first-page":"4688","article-title":"Principal polypeptide target of carcinogen at the beginning of liver carcinogenesis by three carcinogens","volume":"40","author":"Blackburn G. 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