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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IGF-1 and 2 are thought to be important growth factors for breast cancer. However, gene expression of IGFs or IGF receptors in breast cancer tissues, and especially in metastatic breast cancer cells, is not well known. Expression of mRNA encoding for IGF-1, IGF-2, IGF-receptor 1 and 2, IGF binding proteins- 1 to -6, insulin receptor and insulin was determined in the NIH MCF-7 breast cancer cell line, in specimens from breast cancer tissues, and in 6 primary breast cancer cell cultures obtained from metastatic breast cancer, using rT-PCR technique. Specific mRNA sequences encoding for IGF-receptor 1 and 2, IGFBP-2, -4 and insulin receptor were identified in all cell cultures and most of the tissue specimens. Though in most of the tissues additional expression of IGF-1 and IGF-2 was detected, there was no mRNA encoding for these proteins in MCF-7 cell cultures as well as in the primary cell cultures of metastatic breast cancers. In none of our specimens mRNA encoding for IGFBP-1, -3, -5, -6 and insulin was detectable. IGF-receptor expression in cancer tissues and metastatic breast cancer cells supports the hypothesis that IGFs increase tumor cell proliferation in vivo. Expression of IGF-1 and IGF-2 in tumor tissues but not in cancer cell cultures indicates an IGF expression located predominantly in stromal parts of cancer tissues.
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PMID:mRNA expression of components of the insulin-like growth factor system in breast cancer cell lines, tissues, and metastatic breast cancer cells. 961 87

Despite improvements in therapy, the prognosis for advanced breast cancer is poor and a search for new treatment targets and key regulators of tumour growth is warranted. Extensive data are available on the importance of the insulin-like growth factor (IGF) system in growth regulation of breast cancer cell lines in vitro, indicating that the IGF-I receptor (IGF-IR), IGF-I (and IGF-II) function as survival factors, while IGF binding protein (IGFBP)-3 may act as a growth inhibitor. There is a tight link between the growth regulatory pathways of IGFs and oestrogens in oestrogen-receptor(OR)-positive breast cancer cells. In vivo studies indicate a role of IGF-I and IGF-IR in breast cancer development. However, the importance of the IGF system in metastatic and highly aggressive breast tumours in vivo is not clear, and therapeutic strategies designed to interrupt IGF signalling have not yet proved to be an effective treatment modality in patients with metastatic breast cancer.
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PMID:The insulin-like growth factor system in advanced breast cancer. 1468 98

Clinical studies indicate that Herceptin (trastuzumab), a recombinant humanized monoclonal antibody directed against the human epidermal growth factor receptor-2 (HER-2) tyrosine kinase growth factor receptor, provides a significant but transient survival advantage to a subset of patients with HER-2-overexpressing metastatic breast cancer when given as a first-line agent. Increased insulin-like growth factor (IGF)-I receptor (IGF-IR) signaling has recently been identified as a potential factor adversely influencing the response to Herceptin. We examined the effect of recombinant human IGF binding protein 3 (rhIGFBP-3), an antagonist of IGF-IR signaling, in Herceptin-resistant breast cells in vitro and in tumors in vivo. Consistent with results obtained using HER-2- or IGF-IR-transfected cells (MCF-7/HER2-18 and SKBR3/IGF-IR, respectively), we found that rhIGFBP-3 significantly reduced IGF-I-induced IGF-IR phosphorylation and displayed a synergistic interaction with Herceptin against cultured HER-2-overexpressing breast cancer cells in vitro. We show, for the first time, the antitumor activity of rhIGFBP-3 against advanced-stage MCF-7/HER2-18-transfected human breast cancer xenografts and its potentiation of Herceptin activity. We also provide evidence that IGF-IR activation counters the early suppressive effect of Herceptin on HER-2 signaling via Akt and p44/p42 mitogen-activated protein kinase (MAPK), and that inhibition of HER-2-overexpressing human breast tumor growth by rhIGFBP-3 is associated with restored down-regulation of Akt and p44/p42 MAPK phosphorylation in vitro and in vivo. These results emphasize the merit of evaluating simultaneous blockade of the HER-2 and IGF-IR pathways using combination therapy with rhIGFBP-3 plus Herceptin in human clinical trials of patients with HER-2-positive breast cancer.
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PMID:Recombinant human insulin-like growth factor binding protein 3 inhibits growth of human epidermal growth factor receptor-2-overexpressing breast tumors and potentiates herceptin activity in vivo. 1684 73