The role of βIII tubulin in predicting chemoresistance in non-small cell lung cancer

Sève, P.; Reiman, Tony; Dumontet, Charles

doi:10.1016/j.lungcan.2009.09.007

Cited by 76 publications

(64 citation statements)

References 63 publications

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“…1 Nonsmall-cell lung cancer (NSCLC) accounts for »85% of all lung cancer cases. 2 Currently, the most effective therapy for NSCLC is complete lung resection. However, the survival rate after surgery is not satisfactory.…”

Section: Introductionmentioning

confidence: 99%

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Yang

Zhang

Zhao

et al. 2015

Cancer Biology & Therapy

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Background: Lung cancer is the most common cancer that is caused by perturbation of regulatory pathways rather than dysfunction of a single gene. Cisplatin (CDDP; cis-diamminedichloroplatinum II) is the first member of a class of platinum-containing anti-cancer medication, which binds to DNA and triggers apoptosis. CDDP-based chemotherapy is used to treat various types of cancers. However, the efficacy of CDDP in the treatment of non-small-cell lung cancer (NSCLC) is limited by acquired drug resistance. MicroRNAs have recently emerged as key regulators of cancers, and miR-26a is one of downregulated miRNAs in A549/CDDP res cell line. This study aimed to investigate the role of miR-26a in CDDP resistance in NSCLC as well as the underlying mechanisms.Methods: In this study, we analyzed expressional profiles of CDDP resistance-related mRNA, miRNA, and transcription factors (TF) that regulate miRNA expression in NSCLC. A549 cells were treated with CDDP, miR-26a mimic, or miR-26a inhibitor, and followed by biological analysis including drug sensitivity assay, colony formation assay, terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay, and cell cycle analysis. Luciferase assay was used to determine the target of miR-26a. The regulation of miR-26a in Akt pathway was measured by western blot.Results: High mobility group A (HMGA) 2 was identified as the target of miR-26a. Overexpression of miR26a in A549 cells inhibited G1-S transition, increased cell death in response to CDDP treatment, and decreased the colony formation of A549 cells. MiR-26a significantly decreased the expression of E2F1, diminished Akt phosphorylation, and downregulated Bcl2 expression. Cell growth was suppressed by inhibiting HMGA2-mediated E2F1-Akt pathway.Conclusion: MiR-26a is responsible for A549 cell sensitivity in the treatment of CDDP through regulating HMGA2-mediated E2F1-Akt pathway.

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Section: Introductionmentioning

confidence: 99%

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Yang

Zhang

Zhao

et al. 2015

Cancer Biology & Therapy

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“…Rare mutations in b1 tubulin that confer decreased sensitivity to taxanes have been isolated from patients undergoing taxane-based treatment (4). Expression of the bIII isotype of tubulin in cancer cells also confers resistance to microtubule-targeting agents in culture and is a marker of poor prognosis in NSCLC patients (5,6). These mechanisms of resistance negatively impact the primary response of mitotic arrest; however, they are unlikely to account for the majority of NSCLC patients who do not respond to taxane-based therapy.…”

Section: Introductionmentioning

confidence: 99%

Navitoclax Enhances the Efficacy of Taxanes in Non–Small Cell Lung Cancer Models

Tan¹,

Malek²,

Zha³

et al. 2011

Clinical Cancer Research

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Purpose: To explore the potential of navitoclax in combination with taxane-based chemotherapy in the treatment of non-small cell lung cancer (NSCLC) by defining mechanism of synergy and identifying correlative biomarkers.Experimental Design: We treated a panel of NSCLC lines with a dose matrix of paclitaxel and navitoclax (formerly ABT-263), an inhibitor of Bcl-2, Bcl-x L , and Bcl-w (1), and evaluated synergy. We next used timelapse microscopy to explore mechanism of synergy. Finally, we developed an immunohistochemical assay and assessed prevalence of Bcl-x L in NSCLC tumor tissues.Results: All cell lines exhibit greater than additive response to the combination of navitoclax and a taxane. These results were extended to mouse xenograft tumor models, in which the combination is more efficacious than either single-agent docetaxel or navitoclax. Addition of navitoclax to paclitaxel decreases the time from mitotic entry to cell death and changes cell fate from mitotic slippage to death during mitotic arrest. The relative levels of Bcl-x L and Mcl-1 correlate with the extent of synergy, suggesting that cancers with elevated levels of Bcl-x L will be relatively resistant to taxane-based therapy but could benefit from the addition of navitoclax to taxane treatment. Finally, a significant percentage of NSCLC patient samples exhibit relatively high Bcl-x L levels.Conclusions: The addition of navitoclax to taxane-based chemotherapy in NSCLC has the potential to increase efficacy, particularly in patients whose tumors express high levels of Bcl-x L .

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“…Of interest, recent evidence suggests that differential expression of specific β-tubulin isotypes may predict tumor sensitivity/resistance to microtubule-stabilizing agents such as paclitaxel and patupilone in mammalian cells. Consistent with this view, while eight β-tubulin isotypes have been discovered in normal and neoplastic tissues (i.e., classes I, II, III, IVa, IVb, V, VI, and VII) [12,13], overexpression of tubulin β III (TUBB3) has been recently reported in colon [14], breast [15], prostate [16], non-small cell lung [17,18] and ovarian cancers [19,20]. Importantly, in studies in breast and ovarian cancer a significant correlation has been described between higher concentrations of TUBB3 mRNAs and resistance to paclitaxel/docetaxel and sensitivity to patupilone [19][20][21][22].…”

Section: Introductionmentioning

confidence: 73%

Differential in vitro sensitivity to patupilone versus paclitaxel in uterine and ovarian carcinosarcomas cell lines is linked to tubulin-beta-III expression

Roque

Carrara

Cocco

et al. 2012

Gynecologic Oncology

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Objective-To compare the in vitro sensitivity/resistance to patupilone versus paclitaxel in uterine and ovarian carcinosarcomas (CS).Methods-Five primary carcinosarcoma cell lines, two from uterine and three of ovarian origin, were evaluated for growth rate and tested for their in vitro sensitivity/resistance to patupilone versus paclitaxel by MTS assays. To identify potential mechanisms underlying the differential sensitivity/resistance to patupilone, expression levels of β-tubulin III (TUBB3) were determined with quantitative-real-time-polymerase-chain-reaction (q-RT-PCR) in primary uterine and ovarian CS cell lines and in 26 uterine and 9 ovarian CS fresh-frozen-tissues.Results-No appreciable difference in sensitivity to patupilone versus paclitaxel was noted in ovarian CS cell lines, or when uterine and ovarian CS cell lines were compared in their response to paclitaxel. In contrast, uterine CS cell lines were found to be significantly more sensitive to patupilone than to paclitaxel (P < 0.002) and demostrated lower IC 50s to patupilone (range 0.76-0.93 nM) when compared to ovarian CS (range 1.9-3.4 nM, P < 0.05). Higher levels of TUBB3 were detected in uterine CS cell lines and fresh frozen tissues when compared to ovarian CS (P< 0.05).Conclusions-Uterine CS cell lines are significantly more sensitive than ovarian CS cell lines to patupilone versus paclitaxel. High expression of TUBB3 is associated with sensitivity to patupilone in primary CS cell lines and may act as a genetic marker to predict chemotherapy efficacy. Patupilone may represent a promising drug in the treatment of this subset of rare but highly aggressive gynecological tumors.

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The role of βIII tubulin in predicting chemoresistance in non-small cell lung cancer

Cited by 76 publications

References 63 publications

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Navitoclax Enhances the Efficacy of Taxanes in Non–Small Cell Lung Cancer Models

Differential in vitro sensitivity to patupilone versus paclitaxel in uterine and ovarian carcinosarcomas cell lines is linked to tubulin-beta-III expression

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