Association of ATP7A expression and in vitro sensitivity to cisplatin in non-small cell lung cancer

Inoue, Yoshimasa; Matsumoto, H.; Yamada, Shunsuke; Kawai, Kenji; Suemizu, Hiroshi; Gika, Masatoshi; Takanami, Iwao; Iwazaki, Masayuki; Nakamura, Masato

doi:10.3892/ol_00000147

Cited by 28 publications

(24 citation statements)

References 15 publications

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“…In this study, we found that miR-495 increased the intracellular CDDP concentration through the suppression of ATP7A, leading to the sensitivity of NSCLC cells to CDDP. The results are consistent with the previous study that ATP7A is responsible for the CDDP resistance in human NSCLC, ovarian cancer, oral squamous cancer, and epidermoid cancer cells [Kuo et al, 2007;Matsumoto et al, 2007;Yoshizawa et al, 2007;Kalayda et al, 2008;Inoue et al, 2010]. Although one miRNA can regulate more than one target genes, our study, at least partially, illustrated that miR-495 regulated the cell response to CDDP, CBDCA, and L-OHP via the modulation of ATP7A.…”

Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

“…Another study indicates that ATP7A may be responsible for the intracellular cisplatin sequestration during the process of cell resistance to cisplatin in ovarian cancer cells [Kalayda et al, 2008]. In addition, ATP7A is reported to be related to the cisplatin resistance in NSCLC cell lines [Inoue et al, 2010;Li et al, 2012b], but the molecular mechanism responsible for the regulation of ATP7A in NSCLC is yet to be determined. microRNAs (miRNAs) are a class of small non-coding RNA molecules and post-transcriptionally regulate gene expression in various cancers through complete or incomplete complementarity with the binding sites in the 3 0 untranslated region (3 0 UTR) of the target gene mRNA [Bartel, 2004].…”

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confidence: 99%

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miR‐495 Enhances the Sensitivity of Non‐Small Cell Lung Cancer Cells to Platinum by Modulation of Copper‐Transporting P‐type Adenosine Triphosphatase A (ATP7A)

Song

et al. 2014

J of Cellular Biochemistry

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Copper-transporting P-type adenosine triphosphatase A (ATP7A) is associated with platinum drug resistance in non-small cell lung cancer (NSCLC). microRNAs (miRNAs) are a class of small non-coding RNA molecules that regulate gene expression at post-transcriptional level. In this study, the aim is to explore which miRNAs might participate in the platinum resistance by targeting ATP7A in NSCLC. Using real-time PCR-based miRNA expression profiling and bioinformatics, we selected miR-495 as a candidate miRNA. EGFP reporter assay, real-time PCR, and Western blot validated that ATP7A was a direct target for miR-495. The drug sensitivity assay indicated that miR-495 enhanced the cell response to cisplatin (CDDP) in NSCLC cells, while inhibition of miR-495 led to the opposite effects. Importantly, either overexpression or knockdown of ATP7A could override the effect of miR-495 on chemosensitivity. We also demonstrated that miR-495 increased the intracellular CDDP accumulation and overexpression of ATP7A can reduce the increased drug concentration induced by miR-495. Finally, we discovered that there was a converse relationship between miR-495 and ATP7A levels in NSCLC tissues sensitive or resistant to CDDP. In conclusion, our data demonstrate that miR-495 regulates the multi-drug resistance by modulation of ATP7A expression in NSCLC and suggest that miR-495 may serve as a potential biomarker for the treatment of multi-drug resistant NSCLC patients with high ATP7A levels.

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 99%

mentioning

confidence: 99%

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miR‐495 Enhances the Sensitivity of Non‐Small Cell Lung Cancer Cells to Platinum by Modulation of Copper‐Transporting P‐type Adenosine Triphosphatase A (ATP7A)

Song

et al. 2014

J of Cellular Biochemistry

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“…Li et al (29) demonstrated that ATP7A expression was associated with the histological grade of NSCLC and the response to chemotherapy. Inoue et al (30) revealed that ATP7A mRNA expression was useful as a marker for cisplatin chemoresistance in NSCLC. Furthermore, Nakagawa et al (19) found that the ATP7B mRNA and protein levels were significantly increased in human NSCLC cisplatin-resistant xenografts compared with the levels in the cisplatin-sensitive xenografts, indicating that ATP7B was a useful biomarker for platinum resistance in NSCLC.…”

Section: A B Cmentioning

confidence: 99%

Expression of the copper transporters hCtr1, ATP7A and ATP7B is associated with the response to chemotherapy and survival time in patients with resected non-small cell lung cancer

Tian

Chen

et al. 2015

Oncology Letters

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Abstract.Copper transporter family proteins may regulate the chemoresistance of non-small cell lung cancer (NSCLC) to platinum-based anticancer drugs. The present study aimed to investigate the expression of these proteins in lung cancer tissue specimens for association with clinicopathological data and patient responses to chemotherapy and survival. A total of 54 patients with surgically resected NSCLC that received first-line platinum-based doublet chemotherapy were recruited in the present study, and the paraffin-embedded pre-treatment tumor tissue specimens were subjected to immunohistochemical analysis for the expression of human copper transporter 1 (hCtr1) and copper-transporting p-type adenosine triphosphatase 1 (ATP7A) and 2 (ATP7B). This cohort of patients with NSCLC received platinum-based chemotherapy subsequent to the surgical removal of tumor lesions. ATP7B expression was found to be significantly associated with tumor cell differentiation, while hCtr1 expression was significantly associated with improved chemotherapeutic responses. The median survival time was 20 months in patients possessing tumors with high ATP7A expression, but >66 months in patients possessing tumors with low ATP7A expression at the end of the follow-up (P<0.001). The median survival time at the end of the follow-up was 15 months in patients with low tumor hCtr1 expression, but >66 months in patients with high tumor hCtr1 expression (P<0.001). High hCtr1 and low ATP7A expression were each favorable prognostic factors subsequent to chemotherapy for patients with resected NSCLC. Multivariate analysis revealed that high hCtr1 expression combined with low ATP7A expression, good tumor differentiation and female gender were all favorable independent predictive and prognostic factors for patients with resected NSCLC following chemotherapy. High hCtr1 expression combined with low ATP7A expression was associated with an improved prognosis in patients with resected NSCLC that received platinum-based chemotherapy. Surgery combined with neoadjuvant chemotherapy may improve the survival time of patients with NSCLC.

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“…An association between ATP7A expression and in vitro sensitivity to cisplatin was shown in NSCLC. The study revealed significantly higher expression levels of ATP7A mRNA in cisplatin-resistant than in cisplatin-sensitive tumors, and higher expression of ATP7A in the ADC-than in the non-ADC group (Inoue et al, 2010a). High expression of ATP7A led to decreased intracellular cisplatin accumulation in cisplatin-resistant lung ADC cells, and knockdown of ATP7A by siRNA resulted in chemosensitization and induction of apoptosis .…”

Section: Chemoresistance Of Lung Adenocarcinomamentioning

confidence: 90%

Cell death in cancer therapy of lung adenocarcinoma

Zagryazhskaya

Gyurászová²,

Zhivotovsky

2015

Int. J. Dev. Biol.

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Lung cancer is the main cause of all cancer-related deaths in the world, with lung adenocarcinoma (ADC) being the most common subtype of this fatal disease. Lung ADC is often diagnosed at advanced stages involving disseminated metastatic tumors. This is particularly important for the successful development of new cancer therapy approaches. The high resistance of lung ADC to conventional radio-and chemotherapies represents a major challenge to treatment effectiveness. Here we discuss recent progress in understanding the mechanisms of ADC's broad resistance to treatment and its possible therapeutic implications. A number of driving oncogenic alterations were identified in a subset of lung ADCs, making them suitable for targeted therapies directed towards specific cancer-associated molecular changes. In addition, we discuss the molecular aberrations common in lung ADC that are currently being exploited or are potentially important for targeted cancer therapy, as well as limitations of this type of therapy. Furthermore, we highlight possible treatment modalities that hold promise for overcoming resistance to targeted therapies as well as alternative treatment options such as immunotherapies that are potentially promising for improving the clinical outcome of lung ADC patients.

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Association of ATP7A expression and in vitro sensitivity to cisplatin in non-small cell lung cancer

Cited by 28 publications

References 15 publications

miR‐495 Enhances the Sensitivity of Non‐Small Cell Lung Cancer Cells to Platinum by Modulation of Copper‐Transporting P‐type Adenosine Triphosphatase A (ATP7A)

miR‐495 Enhances the Sensitivity of Non‐Small Cell Lung Cancer Cells to Platinum by Modulation of Copper‐Transporting P‐type Adenosine Triphosphatase A (ATP7A)

Expression of the copper transporters hCtr1, ATP7A and ATP7B is associated with the response to chemotherapy and survival time in patients with resected non-small cell lung cancer

Cell death in cancer therapy of lung adenocarcinoma

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