Complexity of expression of the intermediate filaments of six new human ovarian carcinoma cell lines: new expression of cytokeratin 20

Yanagibashi, Takendo; Gorai, Itsuo; Nakazawa, Tomoyuki; Miyagi, Etsuko; Hirahara, Fumiki; Kitamura, Hitoshi; Minaguchi, Hiroshi

doi:10.1038/bjc.1997.471

Cited by 31 publications

(20 citation statements)

References 30 publications

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“…Expression of EGFR and HER in ovarian carcinoma-derived cell lines was assigned to high, moderate, and low categories by consensus of literature [97,106,111,117,187–285]. Association between HER expression and response to inhibitor was determined by contingency table analysis using chi-square or Fisher’s exact test and logistic regression.…”

Section: Figurementioning

confidence: 99%

EGFR/HER-Targeted Therapeutics In Ovarian Cancer

et al. 2012

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Despite decades of research and evolving treatment modalities, survival among patients with epithelial ovarian cancer has improved only incrementally. During this same period, the development of biologically targeted therapeutics has improved survival for patients with diverse malignancies. Many of these new drugs target the human epidermal growth factor receptor (EGFR/HER/ErbB) family of tyrosine kinases, which play a major role in the etiology and progression of many carcinomas, including epithelial ovarian cancer. While several HER-targeted therapeutics are US FDA approved for the treatment of various malignancies, none have gained approval for the treatment of ovarian cancer. Here, we review the published literature on HER-targeted therapeutics for the treatment of ovarian cancer, including novel HER-targeted therapeutics in various stages of clinical development, as well as the challenges that have limited the use of these inhibitors in clinical settings.

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Section: Figurementioning

confidence: 99%

EGFR/HER-Targeted Therapeutics In Ovarian Cancer

et al. 2012

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“…TOV21G and ES2 were obtained from the American Type Culture Collection. SMOV-2 (17), RMG-1 (18), KOC7C (19), HCH1 (20), OVAS (21), OVISE (22), OVTOKO (22), OVMANA (23), OVSAYO (23), and KK (24) were courtesy of Dr. Hiroaki Itamochi (Tottori University School of Medicine, Yonago, Japan; Table 1). Ovarian clear cell carcinoma cell lines were grown in RPMI 1640 with 10% FCS.…”

Section: Methodsmentioning

confidence: 99%

PPM1D Is a Potential Therapeutic Target in Ovarian Clear Cell Carcinomas

Tan

Lambros

Rayter

et al. 2009

Clinical Cancer Research

152

119

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Purpose: To identify therapeutic targets in ovarian clear cell carcinomas, a chemoresistant and aggressive type of ovarian cancer. Experimental Design:Twelve ovarian clear cell carcinoma cell lines were subjected to tiling path microarray comparative genomic hybridization and genome-wide expression profiling analysis. Regions of high-level amplification were defined and genes whose expression levels were determined by copy number and correlated with gene amplification were identified. The effects of inhibition of PPM1D were assessed using short hairpin RNA constructs and a small-molecule inhibitor (CCT007093). The prevalence of PPM1D amplification and mRNA expression was determined using chromogenic in situ hybridization and quantitative real-time reverse transcription-PCR in a cohort of pure ovarian clear cell carcinomas and on an independent series of unselected epithelial ovarian cancers. Results: Array-based comparative genomic hybridization analysis revealed regions of high-level amplification on 1q32, 1q42, 2q11, 3q24-q26, 5p15, 7p21-p22, 11q13.2-q13.4, 11q22, 17q21-q22, 17q23.2,19q12-q13, and 20q13.2.Thirty-four genes mapping tothese regions displayedexpression levels that correlated with copy number gains/amplification. PPM1D had significantly higher levels of mRNA expression in ovarian clear cell carcinoma cell lines harboring gains/amplifications of17q23.2. PPM1D inhibition revealed that PPM1D expression and phosphatase activity are selectively required for the survival of ovarian clear cell carcinoma cell lines with 17q23.2 amplification. PPM1D amplification was significantly associated with ovarian clear cell carcinoma histology (P = 0.0003) and found in10% of primary ovarian clear cell carcinomas. PPM1D expression levels were significantly correlated with PPM1D gene amplification in primary ovarian clear cell carcinomas. Conclusion: Our data provide strong circumstantial evidence that PPM1D is a potential therapeutic target for a subgroup of ovarian clear cell carcinomas.Ovarian clear cell carcinoma accounts for 5% to 13% of all epithelial ovarian carcinomas (1, 2). Compared with other epithelial ovarian carcinoma subtypes, ovarian clear cell carcinomas are associated with a poorer prognosis and a relatively increased resistance to platinum-based chemotherapy (1, 3). Hence, there is a need to identify alternative and/or novel therapeutic approaches for this subgroup of epithelial ovarian carcinomas.Given its relative resistance to conventional chemotherapy, a comprehensive characterization of the molecular genetic features of ovarian clear cell carcinomas could provide clues to the mechanisms of drug resistance and identify novel therapeutic targets (4). In the context of therapeutic target discovery, inhibiting proteins whose expression is driven by gene amplification or activating genetic mutations is an effective approach (5 -7). This concept is best exemplified by the successful use of trastuzumab in the treatment of HER2-amplified breast cancer (8).Previous studies on the molecular fea...

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“…RMG-I c(73) and OVMANA d(74) were obtained from the Health Science Research Resources Bank. The other cell lines were kindly provided as follows: OVISE d (75), OVAS d (76), OVTOKO d (75), and OVSAYO d (74) from Dr. Hiroshi Minaguchi (Yokohama City University, Yokohama, Japan); KK d (77, 78) from Dr. Yoshihiro Kikuchi (National Defense Medical College, Tokorozawa, Japan); and SMOV-2 d (79) from Dr. Tomohiro Iida (St. Marianna University, Kawasaki, Japan).…”

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confidence: 99%

A Link between mir-100 and FRAP1/mTOR in Clear Cell Ovarian Cancer

Nagaraja¹,

Creighton²,

Yu³

et al. 2010

Molecular Endocrinology

220

174

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MicroRNAs (miRNAs) are small noncoding RNAs that direct gene regulation through translational repression and degradation of complementary mRNA. Although miRNAs have been implicated as oncogenes and tumor suppressors in a variety of human cancers, functional roles for individual miRNAs have not been described in clear cell ovarian carcinoma, an aggressive and chemoresistant subtype of ovarian cancer. We performed deep sequencing to comprehensively profile miRNA expression in 10 human clear cell ovarian cancer cell lines compared with normal ovarian surface epithelial cultures and discovered 54 miRNAs that were aberrantly expressed. Because of the critical roles of the phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog 1/mammalian target of rapamycin (mTOR) pathway in clear cell ovarian cancer, we focused on mir-100, a putative tumor suppressor that was the most down-regulated miRNA in our cancer cell lines, and its up-regulated target, FRAP1/mTOR. Overexpression of mir-100 inhibited mTOR signaling and enhanced sensitivity to the rapamycin analog RAD001 (everolimus), confirming the key relationship between mir-100 and the mTOR pathway. Furthermore, overexpression of the putative tumor suppressor mir-22 repressed the EVI1 oncogene, which is known to suppress apoptosis by stimulating phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog 1 signaling. In addition to these specific effects, reversing the expression of mir-22 and the putative oncogene mir-182 had widespread effects on target and nontarget gene populations that ultimately caused a global shift in the cancer gene signature toward a more normal state. Our experiments have revealed strong candidate miRNAs and their target genes that may contribute to the pathogenesis of clear cell ovarian cancer, thereby highlighting alternative therapeutic strategies for the treatment of this deadly cancer.

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Complexity of expression of the intermediate filaments of six new human ovarian carcinoma cell lines: new expression of cytokeratin 20

Cited by 31 publications

References 30 publications

EGFR/HER-Targeted Therapeutics In Ovarian Cancer

EGFR/HER-Targeted Therapeutics In Ovarian Cancer

PPM1D Is a Potential Therapeutic Target in Ovarian Clear Cell Carcinomas

A Link between mir-100 and FRAP1/mTOR in Clear Cell Ovarian Cancer

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