Copper‐transporting P‐type adenosine triphosphatase (ATP7B) as a cisplatin based chemoresistance marker in ovarian carcinoma: Comparative analysis with expression of MDR1, MRP1, MRP2, LRP and BCRP

Nakayama, Kentaro; Kanzaki, Atsuko; Ogawa, Kenji; Miyazaki, Kohji; Neamati, Nouri; Takebayashi, Yuji

doi:10.1002/ijc.10608

Cited by 131 publications

(89 citation statements)

References 33 publications

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“…These proteins are upregulated in cisplatin-resistant cancer cell lines , and their transfection-enforced overexpression has been shown to drive the acquisition of the cisplatin-resistant phenotype . Importantly, clinical studies indicate that ATP7B expression levels might predict the sensitivity of ovarian and endometrial cancers to cisplatin chemotherapy (Nakayama et al, 2002(Nakayama et al, , 2004Aida et al, 2005). Still, in line with the multifactorial nature of cisplatin efflux (and resistance; see below), small molecules that inhibit specific ABC transporters (for example, the P-glycoprotein-specific inhibitor 5-bromotetrandrine) appear to be unable per se to restore cisplatin accumulation and sensitivity (Jin et al, 2005).…”

Section: Mechanisms Of Pre-target Resistancesupporting

confidence: 39%

Molecular mechanisms of cisplatin resistance

et al. 2011

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Platinum-based drugs, and in particular cis-diamminedichloroplatinum(II) (best known as cisplatin), are employed for the treatment of a wide array of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. Cisplatin exerts anticancer effects via multiple mechanisms, yet its most prominent (and best understood) mode of action involves the generation of DNA lesions followed by the activation of the DNA damage response and the induction of mitochondrial apoptosis. Despite a consistent rate of initial responses, cisplatin treatment often results in the development of chemoresistance, leading to therapeutic failure. An intense research has been conducted during the past 30 years and several mechanisms that account for the cisplatin-resistant phenotype of tumor cells have been described. Here, we provide a systematic discussion of these mechanism by classifying them in alterations (1) that involve steps preceding the binding of cisplatin to DNA (pre-target resistance), (2) that directly relate to DNAcisplatin adducts (on-target resistance), (3) concerning the lethal signaling pathway(s) elicited by cisplatin-mediated DNA damage (post-target resistance) and (4) affecting molecular circuitries that do not present obvious links with cisplatin-elicited signals (off-target resistance). As in some clinical settings cisplatin constitutes the major therapeutic option, the development of chemosensitization strategies constitute a goal with important clinical implications.

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Section: Mechanisms Of Pre-target Resistancesupporting

confidence: 39%

Molecular mechanisms of cisplatin resistance

et al. 2011

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“…We have extensively studied mechanisms involved in cisplatin resistance (1,2). Several mechanisms are involved in the acquisition of cisplatin resistance (3), which include reduced drug accumulation (4,5), increased production of cellular thiol (6,7) and augmented DNA repair activity (8,9). We have recently reported that two histone acetyltransferases (HAT), Clock and Tip60, are overexpressed in cisplatin-resistant cells (10,11).…”

Section: Introductionsupporting

confidence: 42%

Enhanced Expression of PCAF Endows Apoptosis Resistance in Cisplatin-Resistant Cells

Hirano

Izumi

Kidani

et al. 2010

Molecular Cancer Research

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Histone acetyltransferase (HAT) regulates transcription. We have previously shown that two HAT genes, Clock and Tip60, are overexpressed, and upregulate glutathione biosynthesis and the expression of DNA repair genes in cisplatin-resistant cells. To better understand the mechanism of HAT-related drug resistance, we investigated the role of another HAT gene, p300/CBP-associated factor (PCAF ), and found that PCAF was also overexpressed in cisplatin-resistant cells and endowed an antiapoptotic phenotype through enhanced E2F1 expression. PCAF-overexpressing cells showed enhanced expression of E2F1 and conferred cell resistance to chemotherapeutic agents. Downregulation of PCAF decreased E2F1 expression and sensitized cells to chemotherapeutic agents. Moreover, knockdown of PCAF induced G 1 arrest and apoptosis. These results suggest that PCAF is one of pleiotropic factors for drug resistance and seems to be critical for cancer cell growth. Mol Cancer Res; 8(6); 864-72. ©2010 AACR.

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“…More convincing has been the demonstration that human tumor cells transfected with ATP7B acquire significant resistance to both cisplatin (ninefold) and copper (twofold), primarily as a consequence of enhanced cisplatin efflux. The recent proposal to use overexpression of ATP7B as a clinical marker of chemoresistance to cisplatin in ovarian cancer affirms the potentially significant role of the copper transporter in cisplatin resistance (Nakayama et al, 2002).…”

Section: Reduced Intracellular Drug Accumulationmentioning

confidence: 40%

Cisplatin: mode of cytotoxic action and molecular basis of resistance

2003

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Cisplatin is one of the most potent antitumor agents known, displaying clinical activity against a wide variety of solid tumors. Its cytotoxic mode of action is mediated by its interaction with DNA to form DNA adducts, primarily intrastrand crosslink adducts, which activate several signal transduction pathways, including those involving ATR, p53, p73, and MAPK, and culminate in the activation of apoptosis. DNA damage-mediated apoptotic signals, however, can be attenuated, and the resistance that ensues is a major limitation of cisplatinbased chemotherapy. The mechanisms responsible for cisplatin resistance are several, and contribute to the multifactorial nature of the problem. Resistance mechanisms that limit the extent of DNA damage include reduced drug uptake, increased drug inactivation, and increased DNA adduct repair. Origins of these pharmacologicbased mechanisms, however, are at the molecular level. Mechanisms that inhibit propagation of the DNA damage signal to the apoptotic machinery include loss of damage recognition, overexpression of HER-2/neu, activation of the PI3-K/Akt (also known as PI3-K/PKB) pathway, loss of p53 function, overexpression of antiapoptotic bcl-2, and interference in caspase activation. The molecular signature defining the resistant phenotype varies between tumors, and the number of resistance mechanisms activated in response to selection pressures dictates the overall extent of cisplatin resistance.

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Copper‐transporting P‐type adenosine triphosphatase (ATP7B) as a cisplatin based chemoresistance marker in ovarian carcinoma: Comparative analysis with expression of MDR1, MRP1, MRP2, LRP and BCRP

Cited by 131 publications

References 33 publications

Molecular mechanisms of cisplatin resistance

Molecular mechanisms of cisplatin resistance

Enhanced Expression of PCAF Endows Apoptosis Resistance in Cisplatin-Resistant Cells

Cisplatin: mode of cytotoxic action and molecular basis of resistance

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