Abstract:
:The insulin like growth factor (IGF) signaling pathway has been shown to contribute to melanoma progression, but little is known about the role of the IGF binding protein 3 (IGFBP-3) in melanoma biology. The aim of the present study was to characterize expression, function and regulation of IGFBP-3 in malignant melanomas and study its potential as a biomarker. The expression of IGFBP-3 varied between different human melanoma cell lines and reintroduction of the protein in non-expressing cells led to induction of apoptosis. Interestingly, in cell lines expressing endogenous IGFBP-3, siRNA silencing of the protein led to a cell line-dependent decrease in proliferation, but had no effect on apoptosis and invasion. Examination of patient material showed that IGFBP-3 is unexpressed in benign nevi while a slight increase in protein expression was seen in primary and metastatic melanoma. However, expression of the protein was low and no correlation was found with circulating levels of IGFBP-3 in serum, suggesting that IGFBP-3 has limited potential as a predictive marker in malignant melanoma. We showed that promoter methylation of IGFBP-3 occurred in both melanoma cell lines and patient material, implicating epigenetic silencing as a regulation mechanism. Furthermore, expression of the protein was shown to be regulated by the PI3-kinase/AKT and MAPK/ERK1/2 pathways. In summary, our findings suggest that IGFBP-3 can exert dual functional effects influencing both apoptosis and proliferation. Development of resistance to the antiproliferative effects of IGFBP-3 may be an important step in progression of malignant melanomas.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Oy GF,Slipicevic A,Davidson B,Solberg Faye R,Maelandsmo GM,Flørenes VAdoi
10.1002/ijc.24727subject
Has Abstractpub_date
2010-01-15 00:00:00pages
350-61issue
2eissn
0020-7136issn
1097-0215journal_volume
126pub_type
杂志文章abstract::Nitric oxide (NO) and its metabolites are implicated in carcinogenesis and metastasis. Both stimulatory and inhibitory effects of NO have been reported in relation to breast cancer and its role in the development of malignancies and metastasis remains uncertain. We have used the polyomavirus middle T antigen (PyV-mT) ...
journal_title:International journal of cancer
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abstract::Parathyroid hormone-related protein (PTHrP) is a causative factor of humoral hypercalcemia in malignancy. However, it is difficult to explain the mechanism of anorexia/cachexia with PTHrP secretion in detail. Previously, we demonstrated that the expressions of orexigenic peptides increased and anorexigenic peptides de...
journal_title:International journal of cancer
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journal_title:International journal of cancer
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doi:10.1002/(sici)1097-0215(19980821)79:4<439::aid-ijc
更新日期:1998-08-21 00:00:00
abstract::In STU mice bearing metastasizing SV40-transformed 51A-232B-M tumors, an immune response against a cellular 60kDa protein (p60) developed in about 50% of the tumor-bearing animals, in addition to the response against SV40 large T-antigen and cellular protein p53. The anti-p60 auto-immune response could be observed as ...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910420620
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journal_title:International journal of cancer
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doi:10.1002/ijc.2910580104
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abstract::Two genes encoding the latent membrane protein 1 (LMP1) of the Epstein-Barr virus (EBV) were isolated from a single case of Hodgkin's disease (HD) and were tested for their biological activities. The LMP1 gene from the Reed-Sternberg cells contained point mutations relative to the prototype LMP1 gene, leading to amino...
journal_title:International journal of cancer
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doi:10.1002/(sici)1097-0215(19980413)76:2<194::aid-ijc
更新日期:1998-04-13 00:00:00
abstract::Although aneuploidy is commonly observed in human cancers, the molecular mechanism underlying aneuploidization remains unclear. We used multiploid cancer model that had diploid and aneuploid cancer cells within the same cancerous tissue and attempted to detect specific epigenetic alterations associated with tumor cell...
journal_title:International journal of cancer
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abstract::We have examined several types of tumor cell lines and shown that they invariably expressed little or no Egr-1, in contrast to their normal counterparts. We have previously shown that the expression of exogenous Egr-1 in human breast and other tumor cells markedly reduces transformed growth and tumorigenicity. We ther...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970703)72:1<102::aid-ijc
更新日期:1997-07-03 00:00:00
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journal_title:International journal of cancer
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doi:10.1002/ijc.20407
更新日期:2004-10-20 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910600614
更新日期:1995-03-16 00:00:00
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journal_title:International journal of cancer
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journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910470410
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journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19991112)83:4<526::aid-ijc
更新日期:1999-11-12 00:00:00
abstract::Human mammary carcinoma cell lines (MCF-7) were analysed for their hormone sensitivity before and after transfection with a v-Ha-ras oncogene or with a neomycin-resistance gene followed by selection in vitro or in vivo. Our aim was to test how the expression of the ras oncogene would influence the estradiol sensitivit...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910460332
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journal_title:International journal of cancer
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doi:10.1002/ijc.22498
更新日期:2007-04-01 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.30220
更新日期:2016-10-15 00:00:00
abstract::A displacement assay with tamoxifen, based on the relative binding affinity of tamoxifen and estradiol for the estrogen receptor (ER), was proposed in 1990 as prognostic indicator for breast-cancer patients. Validation of its predictive results in relation to the outcome of 73 patients with ER+ tumors is analyzed. ER,...
journal_title:International journal of cancer
pub_type: 杂志文章
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abstract::The epithelial ovarian carcinoma (EOC) is an aggressive malignant tumor, and is currently the leading cause of gynecologic cancer death. CA125 is the most commonly used serum marker for EOC, but shows a high-false-positive rate for several benign diseases such as endometriosis. The purpose of our study is therefore to...
journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
pub_type: 杂志文章,评审
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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abstract::Epithelial ovarian cancer (EOC) is a complex disease comprising discrete histological and molecular subtypes, for which survival rates remain unacceptably low. Tailored approaches for this deadly heterogeneous disease are urgently needed. Efflux pumps belonging to the ATP-binding cassette (ABC) family of transporters ...
journal_title:International journal of cancer
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更新日期:2020-10-15 00:00:00