Inhibition of Heat Shock Protein 27–Mediated Resistance to DNA Damaging Agents by a Novel PKCδ-V5 Heptapeptide

Kim, Eun Ho; Lee, Hae June; Lee, Dae Hoon; Bae, Sangwoo; Soh, Jae-Won; Jeoung, Dooil; Kim, Joon; Cho, Chul Koo; Lee, Yoon Jin; Lee, Yun Sil

doi:10.1158/0008-5472.can-06-4344

Cited by 59 publications

(47 citation statements)

References 29 publications

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“…Expression of Hsp27 is upregulated in numerous types of tumors (particularly breast, colon, ovarian and head and neck tumors) and promotes unfavorable outcome (Ciocca and Calderwood, 2005). Overexpression of this protein is frequently associated with increased resistance to radiotherapy and to anti-cancer drugs, such as cisplatin, doxorubicin and etoposide (Hansen et al, 1999;Kim et al, 2007;Zhang and Shen, 2007). Others and we have shown that targeting Hsp27 by antisense strategy increases cancer cell death in vitro and in vivo (Aloy et al, 2008;Matsui et al, 2009).…”

Section: Introductionmentioning

confidence: 86%

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Inhibition of heat shock protein 27 (HspB1) tumorigenic functions by peptide aptamers

et al. 2011

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Section: Introductionmentioning

confidence: 86%

“…Hsp27 has been reported to induce high resistance to some of the drugs used in chemotherapy (Hansen et al, 1999;Kim et al, 2007;Zhang and Shen, 2007). To assess effects of PAs on drug response, HeLa cells transfected with PA11 or PA50 were treated for 18 h with cisplatin or doxorubicin.…”

Section: Inhibition Of Hsp27 Anti-apoptotic Activity By Pas In Hela Cmentioning

confidence: 99%

Inhibition of heat shock protein 27 (HspB1) tumorigenic functions by peptide aptamers

et al. 2011

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“…HSPB1 plays crucial roles in carcinogenesis and progression through inhibition of cell apoptosis and senescence, two essential traits of cancer cells (48 -50). Various human cancers have been reported to exhibit overexpression of HSPB1, and the tumorigenic potentials of HSPB1 have been demonstrated in both experimental animal models and cell biologic studies (51)(52)(53). HSPB1 has been considered as an independent prognosis marker for cancers because its overexpression was involved in chemoradiotherapeutic resistance of tumor cells (54).…”

Section: Knockdown Of Gstp1 Increased the Susceptibility Of Human Bromentioning

confidence: 99%

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

Zeng

Zhang

Deng

et al. 2012

Molecular & Cellular Proteomics

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To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional changes in the carcinogenic process were selectively validated by Western blotting. Immunohistochemistry was performed to detect the expression of the three proteins in an independent set of paraffinembedded archival specimens including various stage tissues of bronchial epithelial carcinogenesis, and their ability for early detection of LSCC was evaluated by receiver operating characteristic analysis. The results showed that the combination of the three proteins could perfectly discriminate NBE from preneoplastic lesions (SM, AH and CIS) from invasive LSCC, achieving a sensitivity of 96% and a specificity of 92% in discriminating NBE from preneoplatic lesions, a sensitivity of 100% and a specificity of 98% in discriminating NBE from invasive LSCC, and a sensitivity of 92% and a specificity of 91% in discriminating preneoplatic lesions from invasive LSCC, respectively. Furthermore, we knocked down GSTP1 in immortalized human bronchial epithelial cell line 16HBE cells, and then measured their susceptibility to carcinogen benzo ( Lung cancer is the most frequently occurring malignancy with increasing incidence and is the leading cause of mortality in cancer-related deaths in China and worldwide (1, 2). Although great improvement has been made in diagnosis and treatment of lung cancer, the overall patients' survival is still very low and does not exceed 15% (3). The poor prognosis of this cancer is mainly explained by the fact that the diagnosis is generally made only at advanced stages because of the lack of reliable, early diagnostic biomarkers and the limited understanding of its carcinogenic mechanisms. Therefore, identification of biomarkers for early detection of lung cancer is mandatory, in turn leading to more effective treatment and reduction of mortality.Lung squamous cell carcinoma (LSCC) 1 originated from the bronchial epithelial cells is the most common histological type of lung cancer. It is known that carcinogenesis of LSCC is a multistage process and the result of multistep accumulation of genetic and epigenetic alterations (4). With exposure to environmental carcinogens, bronchial epithelial carcinogenesis often progresses in the following manner: hyperplasia, squamous metaplasia (SM), atypical hyperplasia (AH), cancer in situ (CIS) and invasive cancer (5). LSCC is the end-point of a whole range of morphological abnormalities that are dis-...

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“…4 It may be necessary to determine the domain of CAGE that interacts with PKC␣ or PKC␦. Heptapeptide derived from the binding domain of PKC␦ to HSP27 was able to restore sensitivity to radiation and cisplatin in NCI-H1299 lung cancer cells (50). This approach could be employed for the development of CAGE-derived peptides to enhance sensitivity to drugs.…”

Section: Discussionmentioning

confidence: 96%

Cancer/Testis Antigen CAGE Exerts Negative Regulation on p53 Expression through HDAC2 and Confers Resistance to Anti-cancer Drugs

Kim

Park

et al. 2010

Journal of Biological Chemistry

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The role of the cancer/testis antigen CAGE in drug resistance was investigated. The drug-resistant human melanoma Malme3M (Malme3M R ) and the human hepatic cancer cell line SNU387 (SNU387 R ) showed in vivo drug resistance and CAGE induction. Induction of CAGE resulted from decreased expression and thereby displacement of DNA methyltransferase 1(DNMT1) from CAGE promoter sequences. Various drugs induce expression of CAGE by decreasing expression of DNMT1, and hypomethylation of CAGE was correlated with the increased expression of CAGE. Down-regulation of CAGE in these cell lines decreased invasion and enhanced drug sensitivity resulting from increased apoptosis. Down-regulation of CAGE also led to decreased anchorage-independent growth. Down-regulation of CAGE led to increased expression of p53, suggesting that CAGE may act as a negative regulator of p53. Down-regulation of p53 enhanced resistance to drugs and prevented drugs from exerting apoptotic effects. In SNU387 R cells, CAGE induced the interaction between histone deacetylase 2 (HDAC2) and Snail, which exerted a negative effect on p53 expression. Chromatin immunoprecipitation assay showed that CAGE, through interaction with HDAC2, exerted a negative effect on p53 expression in Malme3M R cells. These results suggest that CAGE confers drug resistance by regulating expression of p53 through HDAC2. Taken together, these results show the potential value of CAGE as a target for the development of cancer therapeutics.

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Inhibition of Heat Shock Protein 27–Mediated Resistance to DNA Damaging Agents by a Novel PKCδ-V5 Heptapeptide

Cited by 59 publications

References 29 publications

Inhibition of heat shock protein 27 (HspB1) tumorigenic functions by peptide aptamers

Inhibition of heat shock protein 27 (HspB1) tumorigenic functions by peptide aptamers

Identification of Candidate Biomarkers for Early Detection of Human Lung Squamous Cell Cancer by Quantitative Proteomics

Cancer/Testis Antigen CAGE Exerts Negative Regulation on p53 Expression through HDAC2 and Confers Resistance to Anti-cancer Drugs

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