Oncoprotein 18 overexpression increases the sensitivity to vindesine in the human lung carcinoma cells

Nishio, Kazuto; Nakamura, Takashi; Koh, Yasuhiro; Kanzawa, Fumihiko; Tamura, Tomohide; Saijo, Nagahiro

doi:10.1002/1097-0142(20010415)91:8<1494::aid-cncr1157>3.0.co;2-7

Cited by 45 publications

(33 citation statements)

References 17 publications

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“…66 Antimitotic agents that bind to tubulin have been used for chemotherapy to treat various malignancies. Op18 cDNA was transfected to SBC-3 human lung carcinoma cells, and stable transfectants were isolated.…”

Section: Op18 As a Therapeutic Targetcontrasting

confidence: 75%

Identification of novel targets for cancer therapy using expression proteomics

2002

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Although most drugs target proteins, the proteome has remained largely untapped for the discovery of drug targets. The sequencing of the human genome has had a tremendous impact on proteomics and has provided a framework for protein identification. There is currently substantial interest in implementing proteomics platforms for drug target discovery. Although the field is still in the early stages, current proteomic tools include a variety of technologies that could be implemented for large-scale protein expression analysis of cells and tissues, leading to discovery of novel drug targets. Proteomics uniquely allows delineation of global changes in protein expression patterns resulting from transcriptional and post-transcriptional control, post-translational modifications and shifts in proteins between different cellular compartments. Some of the current technologies for proteome profiling and the application of proteomics to the analysis of leukemias by our group are reviewed. Leukemia (2002) 16, 478-485.

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Section: Op18 As a Therapeutic Targetcontrasting

confidence: 75%

Identification of novel targets for cancer therapy using expression proteomics

2002

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“…The presence of multiple transcription factor recognition sequences gives us more confidence of the possibility of a site for PDEF binding on STMN. STMN is overexpressed in many human malignancies including leukemia (42), lymphoma (43), neuroblastoma (44); ovarian (45), prostatic (46), breast (47,48) and lung cancer (49). In many of these cancers, high STMN expression correlates with bad prognosis.…”

Section: Discussionmentioning

confidence: 99%

PDEF downregulates stathmin expression in prostate cancer

et al. 2012

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Abstract. The Ets proteins are a family of transcription factors characterized by an evolutionarily conserved DNA binding domain that controls key cellular processes. Prostate-derived Ets transcription factor (PDEF), a member of the Ets family, is reported to be present in tissues with high epithelial content, notably breast and prostate. However, the role of PDEF in cancer development is not fully understood. To gain insight into the molecular mechanisms associated with prostate cancer progression, we employed iTRAQ labeling followed by mass spectrometric (MS) analysis to identify candidate proteins that are differentially expressed in prostate cancer cells with or without PDEF. To this end, we overexpressed PDEF in PC3 human prostate cells using a tetracycline inducible system (Tet-On). Many differentially expressed proteins which play important roles in various cellular and biological processes were identified. Among them, stathmin (STMN), which is a microtubule (MT)-destabilizing protein, was found to be downregulated in multiple analyses. We demonstrated that re-expression of STMN reversed the antitumor properties of PDEF in PDEF-overexpressing PC3 cells. Using in vitro functional assays, we showed that STMN overexpression counteracted PDEF's effects against cell proliferation, colony formation and tumor migration. Similar results were further confirmed with the prostate cancer cell line CWR22rv1. In conclusion, many differentially expressed proteins were identified and STMN was found to be downregulated by PDEF.These results suggest that PDEF may inhibit prostate cancer progression by transcriptional downregulation of oncogenic STMN expression. Analyzing the association among differentially expressed proteins may provide a basis to better understand the molecular mechanisms underlying the process of cancer progression and development and further aid in designing therapeutics in the future. IntroductionProstate cancer is the most common cancer diagnosed among men and the second leading cause of death in American men, behind only lung cancer. The American Cancer Society (ACS) estimates about 1 man in 36 will die of prostate cancer (1). Although screening for prostate cancer, based on prostate specific antigen (PSA) has revolutionized early detection and diagnosis of the disease, the challenge that clinicians face are to determine which patients progress to aggressive disease (2,3). In order to determine the possibility of disease progression and ability to manage patient outcomes, it is necessary to better understand the molecular processes underlying the disease development and progression. Gene regulation is an important process in maintaining the integrity of cells for their proper growth and survival. Improper regulation of genes can lead to various diseases like cancer. The Ets family of transcription factors has been long investigated for their role in genetic loss of cellular homeostasis which results in development of various cancers. So far, 25 human and 26 murine Ets family members have been report...

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“…Thus, stathmin provides an attractive molecular target for disrupting the mitotic apparatus and arresting the growth of malignant cells. In addition, several studies have shown that stathmin is a potential therapeutic target because a stathmin-transfected lung cancer cell line has increased sensitivity to Vinca alkaloids (Nishio et al, 2001), and antisense inhibition of stathmin expression showed a synergistic apoptotic effect in combination with paclitaxel treatment (Iancu et al, 2000). Further studies with a larger population will improve our ability to treat this cancer.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis

et al. 2006

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Stathmin is an intracellular phosphoprotein that is overexpressed in a number of human malignancies. Our previous study using proteomic profiling showed that significant upregulation of stathmin occurs in oral squamous-cell carcinoma (OSCC)-derived cell lines. In the current study, to determine the potential involvement of stathmin in OSCC, we evaluated the state of stathmin protein and mRNA expression in OSCC-derived cell lines and human primary OSCCs. A significant increase in stathmin expression was observed in all OSCC-derived cell lines examined compared to human normal oral keratinocytes. In immunohistochemistry, 65% of the OSCCs were positive for stathmin, and no immunoreaction was observed in corresponding normal tissues. Real-time quantitative reverse transcriptase -polymerase chain reaction data were consistent with the protein expression status. Moreover, stathmin expression status was correlated with the TNM stage grading. Furthermore, we found a statistical correlation between the protein expression status and disease-free survival (P ¼ 0.029). These results suggest that expression of stathmin could contribute to cancer progression/prognosis, and that stathmin may have potential as a biomarker and a therapeutic target for OSCC.

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Oncoprotein 18 overexpression increases the sensitivity to vindesine in the human lung carcinoma cells

Cited by 45 publications

References 17 publications

Identification of novel targets for cancer therapy using expression proteomics

Identification of novel targets for cancer therapy using expression proteomics

PDEF downregulates stathmin expression in prostate cancer

Overexpression of stathmin in oral squamous-cell carcinoma: correlation with tumour progression and poor prognosis

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