Previous studies showed that 5-fluorouracil (5-FU) is capable of enhancing the membrane reactivity of the human colon carcinoma cell line HT-29 with a monoclonal antibody (COL-I) directed against carcinoembryonic antigen (CEA). In the present study, we show that short-term exposure (i.e., 1 hr) of cancer cells to 5-FU mediates a marked increase of CEA expression, that is concentration-dependent and lasts up to day 5 after treatment. This phenomenon is the result of the drug-mediated enhancement of the CEA expression, but not of the selection of the CEA-positive cells operated by the antimetabolite. This is supported by the finding that the increase of the CEA expression detected by cytofluorimetric analysis is observed not only in the parental HT-29 line, but also in its C22.20 subclone, endowed with a low basal level of CEA and with chemosensitivity to 5-FU lower than that of the parental cell line. Moreover, increase of CEA expression occurs not only in the plasma membrane, but also in the cytosolic cellular compartment, as indicated by the results of Western blot analysis. Northern blot analysis of total RNA extracted from 5-FU-treated HT-29 or C22.20 cells shows an increase in the steady-state levels of CEA and CEA-related transcripts (e.g., biliary glycoprotein). Moreover 5-FU-mediated augmentation of the CEA transcript appears to be attributable mainly to enhanced transcription rather than to increased mRNA stability. it is concluded that induction of enhanced CEA protein expression in cancer cells treated with 5-FU could be of clinical interest for the development of immunochemotherapeutic protocols based on CEA protein as the target molecule.

Prete, S., Aquino, A., Masci, G., Orlando, L., Giuliani, A., De Santis, S., et al. (1996). Drug-induced changes of carcinoembryonic antigen expression in human cancer cells: Effect of 5-fluorouracil. THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 279(3), 1574-1581.

Drug-induced changes of carcinoembryonic antigen expression in human cancer cells: Effect of 5-fluorouracil

PRETE, SALVATORE;AQUINO, ANGELO;DE VECCHIS, LIANA;BONMASSAR, ENZO;GRAZIANI, GRAZIA
1996-01-01

Abstract

Previous studies showed that 5-fluorouracil (5-FU) is capable of enhancing the membrane reactivity of the human colon carcinoma cell line HT-29 with a monoclonal antibody (COL-I) directed against carcinoembryonic antigen (CEA). In the present study, we show that short-term exposure (i.e., 1 hr) of cancer cells to 5-FU mediates a marked increase of CEA expression, that is concentration-dependent and lasts up to day 5 after treatment. This phenomenon is the result of the drug-mediated enhancement of the CEA expression, but not of the selection of the CEA-positive cells operated by the antimetabolite. This is supported by the finding that the increase of the CEA expression detected by cytofluorimetric analysis is observed not only in the parental HT-29 line, but also in its C22.20 subclone, endowed with a low basal level of CEA and with chemosensitivity to 5-FU lower than that of the parental cell line. Moreover, increase of CEA expression occurs not only in the plasma membrane, but also in the cytosolic cellular compartment, as indicated by the results of Western blot analysis. Northern blot analysis of total RNA extracted from 5-FU-treated HT-29 or C22.20 cells shows an increase in the steady-state levels of CEA and CEA-related transcripts (e.g., biliary glycoprotein). Moreover 5-FU-mediated augmentation of the CEA transcript appears to be attributable mainly to enhanced transcription rather than to increased mRNA stability. it is concluded that induction of enhanced CEA protein expression in cancer cells treated with 5-FU could be of clinical interest for the development of immunochemotherapeutic protocols based on CEA protein as the target molecule.
1996
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14 - FARMACOLOGIA
English
Con Impact Factor ISI
antineoplastic agent; carcinoembryonic antibody; carcinoembryonic antigen; dactinomycin; fluorouracil; interferon; monoclonal antibody; antigen expression; antineoplastic activity; article; cancer cell culture; cancer chemotherapy; cancer immunotherapy; cell growth; colon carcinoma; concentration response; controlled study; drug effect; genetic transcription; human; human cell; priority journal; Carcinoembryonic Antigen; Flow Cytometry; Fluorouracil; Gene Expression Regulation, Neoplastic; Humans; RNA, Messenger; Tumor Cells, Cultured
Prete, S., Aquino, A., Masci, G., Orlando, L., Giuliani, A., De Santis, S., et al. (1996). Drug-induced changes of carcinoembryonic antigen expression in human cancer cells: Effect of 5-fluorouracil. THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 279(3), 1574-1581.
Prete, S; Aquino, A; Masci, G; Orlando, L; Giuliani, A; De Santis, S; DE VECCHIS, L; De Filippi, R; Greiner, J; Bonmassar, E; Graziani, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/52721
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