Regulation of insulin-like growth factor binding proteins in ovarian cancer cells by oestrogen

Krywicki, Robert F.; Figueroa, JoséA A.; Jackson, James G.; Kozelsky, Timothy W.; Shimasaki, Shunichi; Hoff, Daniel D. Von; Yee, Douglas

doi:10.1016/0959-8049(93)90464-q

Cited by 31 publications

(14 citation statements)

References 27 publications

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“…As with most other tumor types, clinical trials to date have been limited to small numbers of patients receiving somatostatin analogs. Larger studies, as well as studies employing agents targeting IGF or (192) in 1993 analyzed the effect of estrogen and on IGFBP expression in the estrogen-responsive ovarian cancer cell line PE04. Estrogen decreased the expression of IGFBP-3 mRNA in the cells and also decreased IGFBP-3 peptide levels in the conditioned medium.…”

Section: June 2000mentioning

confidence: 99%

The Effects of Insulin-Like Growth Factors on Tumorigenesis and Neoplastic Growth

2000

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Several decades of basic and clinical research have demonstrated that there is an association between the insulin-like growth factors (IGFs) and neoplasia. We begin with a brief discussion of the function and regulation of expression of the IGFs, their receptors and the IGF-binding proteins (IGFBPs). A number of investigational interventional strategies targeting the GH or IGFs are then reviewed. Finally, we have assembled the available scientific knowledge about this relationship for each of the major tumor types. The tumors have been grouped together by organ system and for each of the major tumors, various key elements of the relationship between IGFs and tumor growth are discussed. Specifically these include the presence or absence of autocrine IGF-I and IGF-II production; presence or absence of IGF-I and IGF-II receptor expression; the expression and functions of the IGFBPs; in vitro and in vivo experiments involving therapeutic interventions; and available results from clinical trials evaluating the effect of GH/IGF axis down-regulation in various malignancies. (Endocrine Reviews 21: 2000)

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Section: June 2000mentioning

confidence: 99%

The Effects of Insulin-Like Growth Factors on Tumorigenesis and Neoplastic Growth

2000

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“…A limited number of genes have already been identified as being estrogen regulated in ovarian cancer. These include genes linked to proliferation (c-myc (Chien et al 1994, Hua et al 1995 and insulin-like growth factor binding proteins (IGFBPs) (Krywicki et al 1993)), differentiation (progesterone receptor (Nash et al 1989, Langdon et al 1994b) and to invasion (CTSD (Galtier-Dereure et al 1992, Rowlands et al 1993) and fibulin-1 (Clinton et al 1996, Moll et al 2002). Two of these genes, namely IGFPB3 and CTSD, were present on the microarray and shown to be modulated by E 2 .…”

Section: Antiach4mentioning

confidence: 99%

“…Estrogen regulation of protein expression has been well documented in breast cancer models but to date little is known about estrogen-regulated gene expression in ovarian cancer. Genes which have been shown to be regulated, thus far, include c-myc (Chien et al 1994, Hua et al 1995, progesterone receptor (Nash et al 1989, Langdon et al 1994b, cathepsin D (CTSD) (GaltierDereure et al 1992, Rowlands et al 1993, fibulin-1 (Clinton et al 1996, Moll et al 2002 and insulin-like growth factor binding proteins (Krywicki et al 1993). …”

Section: Introductionmentioning

confidence: 99%

Estrogen receptor-α mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen

O’Donnell¹,

MacLeod²,

Burns³

et al. 2005

Endocr Relat Cancer

136

131

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Estrogens play a significant role in the development, growth, invasion and metastasis of ovarian tumors. The transcriptional program regulated by 17b-estradiol (E 2 ) in human ovarian cancer cell lines was analyzed using cDNA microarrays containing 1200 cancer-related genes. Twenty-eight transcripts had at least a threefold change in expression in E 2 -treated PEO1 ovarian carcinoma cells compared with controls. These differences were confirmed by real-time quantitative PCR and shown to be dependent upon the expression of functional estrogen receptor-a (ERa). Consistent with this, these gene expression changes were blocked by the anti-estrogen tamoxifen. The use of ERa-and ERb-specific ligands allowed molecular dissection of the E 2 response and showed that ERa activation was responsible for the observed changes in gene expression, whereas ERb played no significant role. Inhibition of de novo protein synthesis by cycloheximide was used to distinguish between primary and secondary target genes regulated by E 2 . Actinomycin D was used to show that changes in gene expression levels induced by E 2 were a result of changes in transcription and not due to changes in mRNA stability. The results presented here demonstrate that estrogen-driven growth of epithelial ovarian carcinoma is mediated by activation of ERa-mediated, and not ERbmediated, transcription.

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“…Tumourderived cell lines including cells from ovarian origin express and produce IGFBP-2 (Yee et al, 1991;Reeve et al, 1992;Hofmann et al, 1994). Ovarian cancer tissues were also shown to express preferentially IGFBP-2 (Krywicki et al, 1993). In the current study we have supplied evidence that the source of the increase in IGFBP-2 levels in body fluids of patients with ovarian malignancy is overproduction of IGFBP-2 by the tumour itself.…”

Section: Igfbp-2 Gene Expressionmentioning

confidence: 99%

Increased insulin-like growth factor binding protein-2 (IGFBP-2) gene expression and protein production lead to high IGFBP-2 content in malignant ovarian cyst fluid

Kanety

Kattan²,

Goldberg³

et al. 1996

Br J Cancer

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Summary Expression of insulin-like growth factor-I (IGF-I), its receptor and IGF-binding proteins (IGFBPs) by ovarian cancer cells and its mitogenic effect on these cells in vitro, suggest that IGF-I may have a role in regulation of human ovarian cancer. We have recently shown IGFBP-2 to be markedly elevated in malignant ovarian cyst fluid in vivo. To identify the origin of increased IGFBP-2 in these cyst fluids, the gene expression and protein content of IGFBP-2 were investigated in 14 malignant and four benign epithelial ovarian neoplasms. IGFBP-2 mRNA was detected in all ovarian specimens and was 2-to 30-fold higher in malignant than in benign neoplasms. Within the malignant tissues IGFBP-2 mRNA levels correlated with the aggressiveness of the tumour and were higher in invasive tumours than in those with borderline pathology. Southern blot analysis revealed no amplification of IGFBP-2 gene in the DNA samples from ovarian tumours regardless of their nature. IGFBP-2 was the major binding protein in tissue extracts, as measured by both Western ligand blotting and immunoblotting, and was significantly higher in malignant than in benign neoplasms. These findings were further supported by immunohistochemical detection of IGFBP-2 in tumour sections. Our data suggest that increased local production by the tumour in vivo is responsible for the increased IGFBP-2 levels in the cyst fluid bathing the ovarian malignancy. This may represent an autocrine regulatory mechanism for IGF-I proliferative effect of ovarian cancer.

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Regulation of insulin-like growth factor binding proteins in ovarian cancer cells by oestrogen

Cited by 31 publications

References 27 publications

The Effects of Insulin-Like Growth Factors on Tumorigenesis and Neoplastic Growth

The Effects of Insulin-Like Growth Factors on Tumorigenesis and Neoplastic Growth

Estrogen receptor-α mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen

Increased insulin-like growth factor binding protein-2 (IGFBP-2) gene expression and protein production lead to high IGFBP-2 content in malignant ovarian cyst fluid

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