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Identification of a Gene Containing Zinc-Finger Motifs Based on Lost Expression in Malignantly Transformed Rat Ovarian Surface Epithelial Cells¹

Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [A.A., A.K.G., P.D.M., L.A.G., D.C.S., T.T., J.R.T., T.C.H.], and Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania 18015 [L.A.G., D.C.S., T.C.H.]

We have used a rat model of epithelial ovarian cancer to identify a gene that shows decreased or lost expression in five of eight independently transformed rat ovarian surface epithelial cell lines compared to the normal progenitor cells. Hence, we refer to this gene as Lot1 (lost on transformation 1; GenBank accession no. U72620). The most abundant transcript of the gene is 6 kb. This sequence contains a 1749-nucleotide open reading frame and, within the 3' untranslated region, 22 near-perfect 60–70-bp repeats and adenine- and uracil-rich areas. The deduced amino acid sequence from the open reading frame contains seven zinc-finger motifs of the C₂H₂ type, as well as proline-, glutamine-, and glutamic acid-rich areas. The gene maps to the short arm of chromosome one in the rat. Lot1 shows a limited distribution of expression in normal rat tissues, including ovary, which shows abundant expression. Furthermore, examination of DNA derived from multiple species indicates that the gene is widely conserved.

¹ The work was supported by NIH Grant CA60643 and a Hoxie Harrison Smith grant (to A. K. G.). T. C. H. was supported by NIH Grant CA56916 and by the Evy Lessin Fund For Ovarian Cancer Research.

² To whom requests for reprints should be addressed, at Department of Medical Oncology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111. Phone: (215) 728-2856; Fax: (215) 728-2741.

Received 1/ 6/97. Accepted 3/24/97.

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