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Expression of rTS Correlates with Altered Growth Regulation of Thymidylate Synthase¹

Department of Experimental Therapeutics, Roswell Park Cancer Institute, Buffalo, New York 14263

The recently discovered rTS gene is convergent with and overlaps the thymidylate synthase gene in the antisense orientation. K562 B1A and KB 1BT are two methotrexate-resistant cell lines that have amplified genes for dihydrofolate reductase. K562 B1A cells have increased levels of rTS mRNA and protein compared with their parental K562 cells, whereas KB 1BT cells show unaltered rTS expression compared with their parental (KB) cells. Altered levels and loss of growth-regulation of in situ thymidylate synthase activity were found in methotrexate-resistant K562 B1A cells but not in K562, KB, and KB 1BT cells. These data point to a link between rTS and the regulation of TS activity.

¹ This work was supported by USPHS Grant CA57634 from the National Cancer Institute and in part by CORE Grant CA16056.

² To whom requests for reprints should be addressed, at Department of Experimental Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. Phone: (716) 845-5828; Fax: (716) 845-8857; E-mail: dolnick@sc3103.med.buffalo.edu.

Received 11/10/95. Accepted 1/ 2/96.

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