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Alternate Splicing of the rTS Gene Product and Its Overexpression in a 5-Fluorouracil-resistant Cell Line¹

Department of Experimental Therapeutics and Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263

rTS is a gene with convergent and overlapping transcription relative to thymidylate synthase (TS). Screening of a cDNA library has identified a second rTS RNA (rTSß) which is related to a previously described rTS RNA (rTS). rTSß differs from rTS by the insertion of an extra 116 nucleotides after base 128 of rTS and an altered 3'-noncoding region such that rTSß RNA is not complementary to TS mRNA. rTS and rTSß RNAs have open reading frames predicted to encode proteins of 361 and 416 amino acids, respectively. Antibody to rTSß protein detects two proteins of the predicted molecular weight in the H630 colon tumor cell line. rTSß is overexpressed 40–70-fold in a 5-fluorouracil-resistant H630 subline compared with 7–8-fold for TS and rTS.

¹ Supported by Grant CA57634 (to B. J. D.) and Core Grant CA16056 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Department of Experimental Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263-0001. Phone: (716) 845-5828; Fax: (716) 845-8857 or 845-8674; E-mail: Dolnick@SC3103.med.buffalo.edu.

Received 4/12/96. Accepted 5/29/96.

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