Multidrug resistance in small cell lung cancer: Expression of P-glycoprotein, multidrug resistance protein 1 and lung resistance protein in chemo-naive patients and in relapsed disease

Triller, Nadja; Korošec, Peter; Kern, Izidor; Košnik, Mitja; Debeljak, A

doi:10.1016/j.lungcan.2006.06.019

Cited by 96 publications

(79 citation statements)

References 20 publications

(21 reference statements)

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“…The characterisation by reporter constructs of the promoter sequences required for these up-and downregulations of ABCB1 in H69 cells is currently under investigation in our laboratory to identify trans-regulatory factors mediating this differential TSA effect. Most drug-resistant lung cancers overexpress both P-gp and MRP1 proteins (Triller et al, 2006). H69VP-resistant cells exhibit upregulation of both MDR proteins, somehow reflecting situations commonly seen in clinic.…”

Section: Discussionmentioning

confidence: 99%

The histone deacetylase inhibitor trichostatin A downregulates human MDR1 (ABCB1) gene expression by a transcription-dependent mechanism in a drug-resistant small cell lung carcinoma cell line model

et al. 2007

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Tumour drug-resistant ABCB1 gene expression is regulated at the chromatin level through epigenetic mechanisms. We examined the effects of the histone deacetylase inhibitor trichostatin A (TSA) on ABCB1 gene expression in small cell lung carcinoma (SCLC) drugsensitive (H69WT) or etoposide-resistant (H69VP) cells. We found that TSA induced an increase in ABCB1 expression in drugsensitive cells, but strongly decreased it in drug-resistant cells. These up-and downregulations occurred at the transcriptional level. Protein synthesis inhibition reduced these modulations, but did not completely suppress them. Differential temporal patterns of histone acetylation were observed at the ABCB1 promoter: increase in H4 acetylation in both cell lines, but different H3 acetylation with a progressive increase in H69WT cells but a transient one in H69VP cells. ABCB1 regulations were not related with the methylation status of the promoter À50GC, À110GC, and Inr sites, and did not result in further changes to these methylation profiles. Trichostatin A treatment did not modify MBD1 binding to the ABCB1 promoter and similarly increased PCAF binding in both H69 cell lines. Our results suggest that in H69 drug-resistant SCLC cell line TSA induces downregulation of ABCB1 expression through a transcriptional mechanism, independently of promoter methylation, and MBD1 or PCAF recruitment.

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Section: Discussionmentioning

confidence: 99%

The histone deacetylase inhibitor trichostatin A downregulates human MDR1 (ABCB1) gene expression by a transcription-dependent mechanism in a drug-resistant small cell lung carcinoma cell line model

et al. 2007

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“…ABCC1 is also able to confer resistance to many chemotherapeutic agents, such as anthracyclines (e.g., doxorubicin) and the folate antagonist methotrexate. Indeed, clinical studies have demonstrated that overexpression of ABCC1 in a variety of solid or invasive tumors, such as breast, ovarian, lung, prostate, and neuroblastoma, is implicated as a high risk factor of MDR and is a negative prognostic biomarker (Filipits et al, 2005;Haber et al, 2006;Triller et al, 2006;Faggad et al, 2009). For example, ABCC1 is readily detectable in all primary neuroblastoma samples studied, and a greater degree of ABCC1 expression is highly predictive of both event-free survival and overall patient survival (Haber et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Small Nucleolar RNA-Derived MicroRNA hsa-miR-1291 Modulates Cellular Drug Disposition through Direct Targeting of ABC Transporter ABCC1

Pan

Zhou

et al. 2013

Drug Metab Dispos

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Multidrug resistance-associated protein 1 (MRP1/ABCC1) is an important membrane transporter that contributes to cellular disposition of many endobiotic and xenobiotic agents, and it can also confer multidrug resistance. This study aimed to investigate the role of human noncoding microRNA-1291 (hsa-miR-1291) in regulation of ABCC1 and drug disposition. Bioinformatics analyses indicated that hsa-miR-1291, localized within the small nucleolar RNA H/ACA box 34 (SNORA34), might target ABCC1 39-untranslated region (39UTR). Using splinted ligation small RNA detection method, we found that SNORA34 was processed into hsa-miR-1291 in human pancreatic carcinoma PANC-1 cells. Luciferase reporter assays showed that ABCC1 39-UTRluciferase activity was decreased by 20% in cells transfected with hsa-miR-1291 expression plasmid, and increased by 40% in cells transfected with hsa-miR-1291 antagomir. Furthermore, immunoblot study revealed that ABCC1 protein expression was sharply reduced in hsa-miR-1291-stably transfected PANC-1 cells, which was attenuated by hsa-miR-1291 antagomir. The change of ABCC1 protein expression was associated with an alternation in mRNA expression. In addition, hsa-miR-1291-directed downregulation of ABCC1 led to a greater intracellular drug accumulation and sensitized the cells to doxorubicin. Together, our results indicate that hsa-miR-1291 is derived from SNORA34 and modulates cellular drug disposition and chemosensitivity through regulation of ABCC1 expression. These findings shall improve the understanding of microRNAcontrolled epigenetic regulatory mechanisms underlying multidrug resistance and interindividual variability in pharmacokinetics.

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“…However, Pgp is also highly expressed in tumors derived from tissues that do not normally express Pgp (36), suggesting that expression of the MDR1 gene may be activated during the conversion to malignancy (7). Moreover, increased Pgp protein and MDR1 gene expression in tumors in cancer patients correlates with resistance to chemotherapeutic agents (43). Indeed, the expression of Pgp in cancer cells has often been associated with poor prognosis and failure of chemotherapy (for reviews, see Refs.…”

mentioning

confidence: 99%

Chemotoxicity of doxorubicin and surface expression of P-glycoprotein (MDR1) is regulated by thePseudomonas aeruginosatoxin Cif

Ye¹,

MacEachran²,

Hamilton³

et al. 2008

American Journal of Physiology-Cell Physiology

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Multidrug resistance in small cell lung cancer: Expression of P-glycoprotein, multidrug resistance protein 1 and lung resistance protein in chemo-naive patients and in relapsed disease

Cited by 96 publications

References 20 publications

The histone deacetylase inhibitor trichostatin A downregulates human MDR1 (ABCB1) gene expression by a transcription-dependent mechanism in a drug-resistant small cell lung carcinoma cell line model

The histone deacetylase inhibitor trichostatin A downregulates human MDR1 (ABCB1) gene expression by a transcription-dependent mechanism in a drug-resistant small cell lung carcinoma cell line model

Small Nucleolar RNA-Derived MicroRNA hsa-miR-1291 Modulates Cellular Drug Disposition through Direct Targeting of ABC Transporter ABCC1

Chemotoxicity of doxorubicin and surface expression of P-glycoprotein (MDR1) is regulated by thePseudomonas aeruginosatoxin Cif

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