Biological Characterization of Human Epithelial Ovarian Carcinoma Cells in Primary Culture: The Insulin-like Growth Factor System

Conover, Cheryl A.; Hartmann, Lynn C.; Bradley, Sarah V.; Stalboerger, Paul G.; Klee, George G.; Kalli, Kimberly R.; Jenkins, Robert B.

doi:10.1006/excr.1997.3861

Cited by 88 publications

(67 citation statements)

References 48 publications

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“…The HOSE cell line was kindly provided by Dr S Mok (E6/E7 immortalized surface ovarian cells stabilized by hTert) (Tsao et al, 1995). OV167 was obtained from Dr C Conover (Conover et al, 1998).…”

Section: Methodsmentioning

confidence: 99%

RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

et al. 2006

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We had previously defined by allele loss studies a minimal region at 6q27 (between D6S264 and D6S297) to contain a putative tumour suppressor gene. The p90 ribosomal S6 kinase-3 gene (p90 Rsk-3, RPS6KA2) maps in this interval. It is a serine-threonine kinase that signals downstream of the mitogen-activated protein kinase pathway. It is expressed in normal ovarian epithelium, whereas reduced or absent in tumours or cell lines. We show that RPS6KA2 is monoallelically expressed in the ovary suggesting that loss of a single expressed allele is sufficient to cause complete loss of expression in cancer cells. Further, we have identified two new isoforms of RPS6KA2 with an alternative start codon. Homozygous deletions were identified within the RPS6KA2 gene in two cell lines. Re-expression of RPS6KA2 in ovarian cancer cell lines suppressed colony formation. In UCI101 cells, the expression of RPS6KA2 reduced proliferation, caused G1 arrest, increased apoptosis, reduced levels of phosphorylated extracellular signal-regulated kinase and altered other cell cycle proteins. In contrast, small interfering RNA against RPS6KA2 showed the opposite effect in 41M cells. The above results suggest that RPS6KA2 is a putative tumour suppressor gene to explain allele loss at 6q27.

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Section: Methodsmentioning

confidence: 99%

RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

et al. 2006

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“…Five of eight ovarian-carcinoma cell lines (OV 167,OV 177,OV 202,OV 207 and OV 266) were low-passage primary lines established at the Mayo Clinic (Conover et al, 1998), whereas OVCAR-5 and SKOV-3 were from American Type Culture Collection (Manassas, VA, USA). All cells were grown according to the providers' recommendations.…”

Section: Cell Culturementioning

confidence: 99%

Epigenetic silencing of HSulf-1 in ovarian cancer:implications in chemoresistance

et al. 2007

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To investigate the mechanism by which HSulf-1 expression is downregulated in ovarian cancer, DNA methylation and histone acetylation of HSulf-1 was analysed in ovarian cancer cell lines and primary tumors. Treatment of OV207 and SKOV3 by 5-aza-2 0 -deoxycytidine resulted in increased transcription of HSulf-1. Sequence analysis of bisulfite-modified genomic DNA from ovarian cell lines and primary tumors without HSulf-1 expression revealed an increase in the frequency of methylation of 12 CpG sites in exon 1A. Chromatin immunoprecipitation assays showed an increase in histone H3 methylation in cell lines without HSulf-1 expression. To assess the significance of HSulf-1 downregulation in ovarian cancer, OV167 and OV202 cells were transfected with HSulf-1 siRNA. Downregulation of HSulf-1 expression in OV167 and OV202 cells lead to an attenuation of cisplatin-induced cytotoxicity. Moreover, patients with ovarian tumors expressing higher levels of HSulf-1 showed a 90% response rate (27/30) to chemotherapy compared to a response rate of 63% (19/30) in those with weak or moderate levels (P ¼ 0.0146, v 2 test). Collectively, these data indicate that HSulf-1 is epigenetically silenced in ovarian cancer and that epigenetic therapy targeting HSulf-1 might sensitize ovarian tumors to conventional first-line therapies.

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“…4 Ovarian cancer cells express not only IGFs and IGF-1 receptor, but also several isoforms of IGFBPs. 8,9 Among the IGFBPs expressed in ovarian cancers, IGFBP2 is markedly increased and significantly higher in cystic fluid from malignant epithelial ovarian tumors than in cystic fluid from benign epithelial ovarian tumors, mainly due to the increase in mRNA and protein expression in the tumor cells. 10 Serum IGFBP2 levels are also significantly higher in patients with ovarian cancer compared with benign controls.…”

mentioning

confidence: 99%

“…9 However, its role in tumorigenesis, if any, is not clear at this time. It has been reported that IGFBP5 promoted the growth of prostate cancer cells in vitro and accelerated the progression to androgen independence in prostate cancer animal models.…”

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confidence: 99%

Insulin-like growth factor-binding protein 2 and 5 are differentially regulated in ovarian cancer of different histologic types

et al. 2006

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The family of insulin-like growth factor-binding proteins (IGFBPs) comprises six members, which bind and regulate the functions of insulin-like growth factors. Overexpression of IGFBP2 and IGFBP5 contributes to the invasiveness and progression of several human cancers, but their role and clinical significance in ovarian cancer has not been investigated in detail. We examined IGFBP2 and IGFBP5 expression levels using two tissue microarrays, one containing six normal surface epithelium, six benign serous cysts, 10 serous borderline tumors, eight low-grade, and 20 high-grade serous carcinomas. The other comprising 441 ovarian cancers of different histologic types linked to a clinicopathologic database. Each tumor was sampled in duplicate with a 1.0-mm punch core needle. Immunohistochemical staining was performed using antibodies against IGFBP2 or IGFBP5. The staining intensity was scored semiquantitatively as negative (0), weak (1-10%), moderate (10-50%), or strong (50-100%) using computerized image analysis. Statistical analyses used Fisher's exact test and Kaplan-Meier method. IGFBP2 and IGFBP5 were overexpressed in high-grade serous carcinomas compared to normal surface epithelium, benign serous cysts, serous borderline tumors, or low-grade serous carcinoma. They were differentially expressed in different types of ovarian carcinomas, being more often expressed at high levels in high-grade serous carcinoma, malignant mixed mullerian tumors and undifferentiated carcinoma, and more often expressed at low levels or not at all in clear cell and mucinous carcinomas. We concluded that IGFBP2 and IGFBP5 might play a role in the development of high-grade ovarian serous carcinoma, but not in mucinous or clear cell ovarian carcinomas.

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Biological Characterization of Human Epithelial Ovarian Carcinoma Cells in Primary Culture: The Insulin-like Growth Factor System

Cited by 88 publications

References 48 publications

RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

Epigenetic silencing of HSulf-1 in ovarian cancer:implications in chemoresistance

Insulin-like growth factor-binding protein 2 and 5 are differentially regulated in ovarian cancer of different histologic types

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