Association of RNA with thymidylate synthase from methotrexate-resistant Streptococcus faecium.

Expression of rTS correlates with altered growth regulation of thymidylate synthase.

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 co...

Antitumor activity of antifolate inhibitors of thymidylate and purine synthesis in human soft tissue sarcoma cell lines with intrinsic resistance to methotrexate.

We examined the antitumor effects of two antifolate inhibitors of thymidylate synthesis, N-(5-[N-(3, 4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino ]-2-theno yl-L-glutamic acid (D1694; Tomudex) and 1843U89 as well as a folate-based inhibitor of purine synthesis, 5, 10-dideazatetrahydrofolic acid (DDATHF) on human soft tissue sarcoma cell lines having intrinsic resistance to methot...

Presence of conjugase activity in amethopterin-resistant Streptococcus faecium.

Overproduction of a bifunctional thymidylate synthetase-dihydrofolate reductase and DNA amplification in methotrexate-resistant Leishmania tropica.

Leishmania tropica promastigotes that are highly resistant to methotrexate, a dihydrofolate reductase inhibitor, have been developed. Organisms resistant to 1 mM methotrexate have a 40-fold increase in dihydrofolate reductase which is associated with thymidylate synthetase, and they contain amplified regions of DNA that may be directly visualized on stained gels of restriction digests. The ampl...

Cloning and characterization of a naturally occurring antisense RNA to human thymidylate synthase mRNA.

Based upon reverse transcription and polymerase chain reaction results with human KB cell RNA, a cDNA (i.e., 3'rTS1, 1557 nt) with complementarity to thymidylate synthase mRNA was cloned and sequenced. Northern blot analysis showed that 3'rTS1 corresponded to a cytoplasmic 1.8 kb RNA found in several tumor cell lines. The remaining 5'region of this antisense RNA was cloned by a RACE (Rapid Ampl...