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J. Suzanne Lindsey1 *
Department of Pharmaceutical Sciences, Texas Tech University, Amarillo, TX. 1
Scatter factor (SF) mRNA expression in the nonhuman primate endometrium is downregulated by progesterone. In other tissues, SF has been shown to cause cell migration. SF acts on the tyrosine kinase protooncogene receptor, MET, which, in turn, signals through the Rac, Ras, and STAT pathways. However, little is known about the early genes that need to be transcribed for migration to occur. Treatment of primary endometrial epithelial cells with SF in vitro has been shown to cause migration and lumen formation. Migration of MET positive luminal and glandular epithelial cells in the endometrium occur predominantly during days 3 to 5 of the human menstrual cycle. In an effort to determine the mechanism by which SF functions in the endometrium, specific genes upregulated after stimulation with SF were isolated. We utilized an in vitro system including an immortalized endometrial epithelial cell line, RL-95, the active form of SF (also known as hepatocyte growth factor) and suppression subtraction hybridization (SSH). By Northern analysis of total mRNA, one clone isolated, RL95-7, upregulates within two hours after SF stimulation of RL95 cells, a time frame before migration commences. Expression of this transcript decreases to almost undetectable levels by 50 hours after stimulation. Comparison of the sequence for this cDNA clone with the Genbank database by BLAST and FASTA analyses shows no homology; indicating that this is a novel gene. In addition, by Northern blot analysis of poly A+ RNA, this novel transcript is not detectably expressed in placenta, prostate, muscle, spleen, liver, lung, maxillary gland, myometrium, or 14 day estrogen-treated endometrium. These results suggest that the novel cDNA is regulated by SF/MET, is expressed in a cell- and tissue-specific manner and precedes migration of endometrial epithelial cells in vitro.
This abstract is being presented on Tuesday, August 3 at 5:30 PM at Todd 130.