Evaluation of MDR1, LRP, MRP, and topoisomerase IIalpha gene mRNA transcripts before and after interferon-alpha, and correlation with the mRNA expression level of the telomerase subunits hTERT and TEP1 in five unselected human melanoma cell lines.

Clelia Miracco, Emilia Maellaro, Lorenzo Pacenti, Barbara Del Bello, Marta A. Valentini, Pietro Rubegni, Luigi Pirtoli, Chiara Volpi, Rosa Santopietro, Piero Tosi

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Abstract

Intrinsic and acquired multidrug-resistance (MDR) and the activity of the enzyme telomerase have been demonstrated in human melanoma. A direct regulation of the MDR pathways and of telomerase by interpheron-alpha (IFN-alpha), which is currently used in the therapy of advanced cutaneous melanoma, has also been hypothesized. In this study, we used five melanoma cell lines not selected in vitro for drug resistance (Me665/2/21, Me665/2/60, HT-144, SK-MEL-28, and SK-MEL-5), which in a previous study, had shown different responses to IFN-alpha in terms of proliferation, apoptosis, telomerase activity and expression of mRNA for the human telomerase reverse transcriptase (hTERT). We investigated the expression of the multidrug resistance (MDR1) gene, multidrug resistance protein (MRP), lung resistance protein (LRP), topoisomerase IIalpha (Topo IIalpha), hTERT, and telomerase-associated protein (TEP1), which is shared by telomerase and vault MDR proteins at the mRNA expression level, using the reverse transcription-PCR (RT-PCR). All cell lines showed an intrinsic expression of hTERT, TEP1, and MDR gene transcripts (only MDR1 mRNA was under the detection level in SK-MEL-28 cells). After IFN-alpha exposure, we observed either no effect, a trend towards a decrease of hTERT, MRP, and Topo IIalpha, or an increase of TEP1, MDR1, and LRP mRNA expression in some cell lines. Effects were usually temporary and not always significant. No correlation was found between hTERT and TEP1 mRNA expression, whereas significant positive correlations were found between TEP1 and MDR1 mRNA, and between TEP1 and LRP mRNA. IFN-alpha modulates differently MDR gene transcripts in human melanoma cell lines. Positive correlation between TEP1 and LRP also seems to identify them as common targets of IFN-alpha effects.

Original languageEnglish
Pages (from-to)213-220
Number of pages8
JournalInternational Journal of Oncology
Volume23
Issue number1
Publication statusPublished - Jul 2003

Fingerprint

P-Glycoproteins
Telomerase
Interferon-alpha
Melanoma
Cell Line
Messenger RNA
MDR Genes
Genes
Multiple Drug Resistance
major vault protein
human TERT protein
Drug Resistance
Reverse Transcription
Apoptosis
Polymerase Chain Reaction
Skin
Enzymes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Evaluation of MDR1, LRP, MRP, and topoisomerase IIalpha gene mRNA transcripts before and after interferon-alpha, and correlation with the mRNA expression level of the telomerase subunits hTERT and TEP1 in five unselected human melanoma cell lines. / Miracco, Clelia; Maellaro, Emilia; Pacenti, Lorenzo; Del Bello, Barbara; Valentini, Marta A.; Rubegni, Pietro; Pirtoli, Luigi; Volpi, Chiara; Santopietro, Rosa; Tosi, Piero.

In: International Journal of Oncology, Vol. 23, No. 1, 07.2003, p. 213-220.

Research output: Contribution to journalArticle

Miracco, Clelia ; Maellaro, Emilia ; Pacenti, Lorenzo ; Del Bello, Barbara ; Valentini, Marta A. ; Rubegni, Pietro ; Pirtoli, Luigi ; Volpi, Chiara ; Santopietro, Rosa ; Tosi, Piero. / Evaluation of MDR1, LRP, MRP, and topoisomerase IIalpha gene mRNA transcripts before and after interferon-alpha, and correlation with the mRNA expression level of the telomerase subunits hTERT and TEP1 in five unselected human melanoma cell lines. In: International Journal of Oncology. 2003 ; Vol. 23, No. 1. pp. 213-220.
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abstract = "Intrinsic and acquired multidrug-resistance (MDR) and the activity of the enzyme telomerase have been demonstrated in human melanoma. A direct regulation of the MDR pathways and of telomerase by interpheron-alpha (IFN-alpha), which is currently used in the therapy of advanced cutaneous melanoma, has also been hypothesized. In this study, we used five melanoma cell lines not selected in vitro for drug resistance (Me665/2/21, Me665/2/60, HT-144, SK-MEL-28, and SK-MEL-5), which in a previous study, had shown different responses to IFN-alpha in terms of proliferation, apoptosis, telomerase activity and expression of mRNA for the human telomerase reverse transcriptase (hTERT). We investigated the expression of the multidrug resistance (MDR1) gene, multidrug resistance protein (MRP), lung resistance protein (LRP), topoisomerase IIalpha (Topo IIalpha), hTERT, and telomerase-associated protein (TEP1), which is shared by telomerase and vault MDR proteins at the mRNA expression level, using the reverse transcription-PCR (RT-PCR). All cell lines showed an intrinsic expression of hTERT, TEP1, and MDR gene transcripts (only MDR1 mRNA was under the detection level in SK-MEL-28 cells). After IFN-alpha exposure, we observed either no effect, a trend towards a decrease of hTERT, MRP, and Topo IIalpha, or an increase of TEP1, MDR1, and LRP mRNA expression in some cell lines. Effects were usually temporary and not always significant. No correlation was found between hTERT and TEP1 mRNA expression, whereas significant positive correlations were found between TEP1 and MDR1 mRNA, and between TEP1 and LRP mRNA. IFN-alpha modulates differently MDR gene transcripts in human melanoma cell lines. Positive correlation between TEP1 and LRP also seems to identify them as common targets of IFN-alpha effects.",
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AU - Miracco, Clelia

AU - Maellaro, Emilia

AU - Pacenti, Lorenzo

AU - Del Bello, Barbara

AU - Valentini, Marta A.

AU - Rubegni, Pietro

AU - Pirtoli, Luigi

AU - Volpi, Chiara

AU - Santopietro, Rosa

AU - Tosi, Piero

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