Constitutive Expression of Multiple Growth Factor Genes by Melanoma Cells but Not Normal Melanocytes

Rodeck, Ulrich; Melber, Karl; Kath, R.; Menssen, Hans-Dietrich; Varello, Michael; Atkinson, Barbara; Herlyn, Meenhard

doi:10.1111/1523-1747.ep12477822

Cited by 152 publications

(86 citation statements)

References 43 publications

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“…Although Rodeck et al 51 found that IGF-1 is not expressed in melanoma cells, Kanter-Lewensohn and coworkers 49 showed that IGF-1R expression is correlated with melanoma progression, suggesting that paracrine-derived signals may determine IGF-1R activation during melanoma progression. In addition, Satyamoorthy et al 47 found that fibroblast-derived IGF-1 promotes growth and survival of early-stage melanoma cells.…”

Section: In Vitro and In Vivo Experimental Data: Igf-1 Molecular Signmentioning

confidence: 99%

Insulin-Like Growth Factor System and Sporadic Malignant Melanoma

Capoluongo¹

2011

The American Journal of Pathology

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Insulin and insulin-like growth factors (IGFsMelanoma is a malignant tumor originating from melanocytes, the melanin-producing cells.1,2 During fetal development, melanocytes migrate to different body areas, such as the skin, uvea, leptomeninges, and mucous membranes (eg, upper esophagus, vulva, and anus).2 Although melanoma may arise in all these sites, cutaneous melanoma is by far the most frequent type of melanoma, representing approximately 5% to 7% of all skin malignancies and the most lethal skin cancer (approximately 75% of all deaths from skin tumors).2,3 The following melanoma risk factors have been extensively described: i) sun exposure, ii) presence of dysplastic nevi, iii) age, iv) ethnicity, v) personal or family history of melanoma, vi) phototype, vii) presence of xeroderma pigmentosum, viii) Li-Fraumeni syndrome, ix) hereditary retinoblastoma history, and x) immunosuppressive conditions. 4 In addition to environmental and individual risk factors, the genetic pedigree may also represent a further risk factor for melanoma development; indeed, multiple differences between melanoma cell genomes and those of normal melanocytes were identified in genomewide analysis studies. In particular, point mutations, deletions, gene amplifications and translocations, and/or epigenetic modifications (eg, promoter hypermethylation) appear to be associated with a significant growth advantage, as opposed to normal skin cells. 5 Furthermore, many molecular changes have been reported in advanced stages of melanoma, as opposed to normal melanocytes. The most common mutations are as follows: i) protoncogene serine/threonine kinase B-Raf-activating mutations, 6 ii) E-cadherin expression silencing, 7 and iii) telomerase activity acquisition, 8 followed by hundreds more, identified by comparative gene expression profiling of melanomas with various American Joint Committee on Cancer stages. 1,9,10 A recent article by Bennet 1 provided a detailed list of possible genes involved in melanoma spreading and development.Along with all pathways and molecules studied in different cancers, including melanoma itself, the study of the insulin-like growth factor (IGF) network of ligands, cell surface receptors, and IGF-binding proteins (IGFBPs; eg, the IGF-1 system) have attracted considerable interest because these pathways play important roles at multiple levels, from cellular and organ to organism.11-13 The IGF system mediates growth, differentiation, and developmental processes; it is involved in a variety of metabolic activities.13 Deregulation of IGF system expression and action is linked to several pathological features, ranging from growth deficits to cancer development. TarSupported by the Italian Health Ministry (code ONC_ORD3207) and Programma strategico 3: Diagnostica ad elevata complessità e tecnologie per il monitoraggio di pazienti con patologie croniche-PROGETTO 4_ISS.Accepted for publication August 10, 2010. CME Disclosure: The author did not disclose any relevant financial relationships.Address reprint requests to Ettor...

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Section: In Vitro and In Vivo Experimental Data: Igf-1 Molecular Signmentioning

confidence: 99%

Insulin-Like Growth Factor System and Sporadic Malignant Melanoma

Capoluongo¹

2011

The American Journal of Pathology

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“…Human neonatal foreskin keratinocyte cultures were initiated and propagated in an MCDB base medium (MCDB153, Sigma) containing 30 mM Ca 2+ supplemented with ethanolamine, phosphorylethanolamine, hydrocortisone, insulin, puri®ed EGF, and bovine pituitary extract, as previously described in detail (McNeill and Jensen, 1990). HaCaT, A431, and SCC cells were grown in W489 medium consisting of four parts of MCDB153 and one part L15 media supplemented with 2% fetal bovine serum (Rodeck et al, 1991). To inhibit EGFR activation, cells were treated for 2 ± 4 days with mAb 425 (10 mg/ml), control mAb BR15-6A (10 mg/ml), AG1478 (10 mM), or control AG1295 (10 mM) as previously described (Jost et al, 1999).…”

Section: Cell Lines and Tissuesmentioning

confidence: 99%

Metastasis-associated protein (MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human keratinocytes

et al. 2002

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The human metastasis-associated gene (MTA1), a member of the nucleosome remodeling complex with histone deacetylase activity, is frequently overexpressed in biologically aggressive epithelial neoplasms. Here, we extend this observation to squamous carcinoma cells, which express high levels of MTA1 relative to normal or immortalized keratinocytes. To address functional aspects of MTA1 expression, we established variants of human immortalized keratinocytes (HaCaT cells) by expressing MTA1 cDNA in both the sense and antisense orientations. We demonstrate that (1) forced MTA1 expression enhances migration and invasion of immortalized keratinocytes; (2) MTA1 expression is necessary but not su cient for cell survival in the anchorage independent state; (3) MTA1 contributes to expression of the anti-apoptotic Bcl-2 family member Bcl-x L ; (4) MTA1 expression in immortalized keratinocytes depends, in part, on activation of the epidermal growth factor receptor (EGFR). These results establish that, in keratinocytes, MTA1 expression contributes to several aspects of the metastatic phenotype including survival in the anchorage independent state, migration, and invasion.

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“…Constitutive expression of TGFalpha, inducing stimulation of EGFR homodimers as well as EGFR/ HER2 heterodimers is a late event in human melanoma development resulting in autocrine growth signalling (Rodeck et al, 1991). Noteworthy, whereas expression of HER2 is found in melanocytes as well as in melanoma (Peris et al, 1991), the expression level of EGFR correlates with melanoma progression and is not found in melanocytes (Rodeck et al, 1991).…”

Section: Homodimers Of the Mrk Kinase Act As Potent Growth Factor Recmentioning

confidence: 99%

“…Noteworthy, whereas expression of HER2 is found in melanocytes as well as in melanoma (Peris et al, 1991), the expression level of EGFR correlates with melanoma progression and is not found in melanocytes (Rodeck et al, 1991). This together with the fact that melanocytes transformed by neu but lacking EGFR expression are not tumorigenic (Dotto et al, 1989) may re¯ect that in human melanoma receptors of the EGFR family trigger cell transformation as heterodimers.…”

Section: Homodimers Of the Mrk Kinase Act As Potent Growth Factor Recmentioning

confidence: 99%

Activation of STAT5 triggers proliferation and contributes to anti-apoptotic signalling mediated by the oncogenic Xmrk kinase

et al. 2002

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Extensive studies of primary tumors and tumor derived cell lines revealed that inappropriate activation of speci®c STATs (particularly of STAT3 and STAT5) occurs with high frequency in a wide variety of human cancers. We reported recently that the melanoma inducing EGFRrelated receptor Xmrk speci®cally induces constitutive activation of STAT5 in ®sh melanoma cells. However, little is known about the role of STAT5 in solid tumours in general and its function in melanoma in particular. Recent examinations suggest that activated STAT signalling participates in oncogenesis by stimulating cell proliferation and preventing apoptosis. As an initial approach to understanding the consequences of Xmrk induced STAT5 signalling we used the well characterized pro B-cell line Ba/F3 as a sensitive system to analyse mitogenic as well as anti-apoptotic signalling. We identi®ed STAT5 activation as being involved in both growth and survival signalling triggered by the Xmrk kinase possibly due to STAT5 induced expression of pim-1 and bcl-x. We also found a new mechanism of activation of STAT5 by receptor tyrosine kinases, whereby direct interaction of the receptor kinase domain with the STAT protein in a phosphotyrosine independent way led to activation of STAT5 in terms of DNA binding and target gene expression.

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Constitutive Expression of Multiple Growth Factor Genes by Melanoma Cells but Not Normal Melanocytes

Cited by 152 publications

References 43 publications

Insulin-Like Growth Factor System and Sporadic Malignant Melanoma

Insulin-Like Growth Factor System and Sporadic Malignant Melanoma

Metastasis-associated protein (MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human keratinocytes

Activation of STAT5 triggers proliferation and contributes to anti-apoptotic signalling mediated by the oncogenic Xmrk kinase

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