title: Expression of rTSbeta as a 5-fluorouracil resistance marker in patients with primary breast cancer.
abstract: Expression of thymidylate synthase (TS) in tumor cells is frequently suggested as an important prognostic factor for patients scheduled for chemotherapy with 5-fluorouracil (5-FU). However, clinical evidence does not fully support such an anticipation. We studied the expression of rTSbeta, a reverse orientation gene of TS, as a 5-FU resistance marker in patients with primary breast cancer. Expression of rTSbeta was examined in 129 patients with newly diagnosed breast cancer and five breast cancer cell lines by immunohistochemistry, immunocytochemistry and immunoblotting. Clinically, expression of rTSbeta was found to correlate with survival of the patients (p=0.023) when patients received chemotherapeutic regimen containing 5-FU. In vitro, rTSbeta expression was found to correlate with 5-FU resistance in breast cancer cell lines. Notably, in the 5-FU-resistant cells, rTSbeta was identified in the nucleus, whereas in the 5-FU-sensitive cells, rTSbeta was found in the cytoplasm. Nuclear localization of rTSbeta was further found to be associated with protein farnesylation. Therefore, nuclear expression of rTSbeta could be a novel 5-FU resistance marker in patients with primary breast cancer.
authors: Department of Research, Surgical Research Laboratory, Chang-Hua Christian Hospital, Taiwan, ROC.
authors: Shou-Jen
authors: SJ
authors: Kuo
authors: Hwei-Chung
authors: HC
authors: Wang
authors: Kuan-Chih
authors: KC
authors: Chow
authors: Shiow-Her
authors: SH
authors: Chiou
authors: Shu-Fen
authors: SF
authors: Chiang
authors: Tze-Yi
authors: TY
authors: Lin
authors: I-Ping
authors: IP
authors: Chiang
authors: Dar-Ren
authors: DR
authors: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D016375:Antisense Elements (Genetics); D015415:Biomarkers; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D011090:Polyenes / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D054876:Prenylation; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology
chemical_list: D000964:Antimetabolites, Antineoplastic; D016375:Antisense Elements (Genetics); D015415:Biomarkers; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D013940:Thymidylate Synthase; C054474:manumycin; D005472:Fluorouracil