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Radial Growth Phase Melanomas (radial + growth_phase_melanoma)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Predominant formation of heavily pigmented dermal melanocytomas resembling ,animal-type' melanomas in hepatocyte growth factor (C57BL/6 × C3H)F1 mice following neonatal UV irradiation

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2007
Scott R. Florell
Background:, Transgenic mice expressing hepatocyte growth factor (HGF) develop cutaneous melanocytic tumors following neonatal UV exposure. Here, we examined the histologic spectrum of UV-induced melanocytic tumors in HGF mice on a pigmented (C57BL/6 × C3H/HeN)F1 background. Methods:, Neonatally irradiated (4000 J/m2) mice were monitored for 43 weeks, and 31/34 (91%) animals developed a total of 163 melanocytic tumors. Results:, Of 54 primary tumors analyzed, most (49/54, 91%) demonstrated exclusively dermal collections of epithelioid cells with voluminous densely pigmented cytoplasm. Seven of these also demonstrated a population of spindled cells with mitoses. Several (3/54, 6%) tumors exhibited a junctional component with melanocytes present in the epidermis. Staining with PEP8 confirmed the presence of interfollicular melanocytes at the dermal-epidermal junction in neonatal skin. Conclusions:, In contrast to HGF animals on an albino (FVB) background, HGF animals on the pigmented (C57BL/6 × C3H/HeN)F1 background do not develop classic radial growth phase melanoma but rather predominantly develop dermal melanocytomas resembling the ,animal-type' melanoma occasionally seen in humans. These results demonstrate the influence of genetic background on histologic pattern of UV-induced melanomas in mice. [source]

Id1 expression is transcriptionally regulated in radial growth phase melanomas

INTERNATIONAL JOURNAL OF CANCER, Issue 8 2007
Byungwoo Ryu
Abstract Id genes have been demonstrated to be upregulated in a wide variety of human malignancies and their expression has been correlated with disease prognosis; however, little is known about the mechanisms of Id gene activation in tumors. We have previously shown that the helix-loop-helix transcription factor, Id1, is highly expressed in primary human melanomas during the radial growth phase and that Id1 is a transcriptional repressor of the familial melanoma gene CDKN2A. Here we use a series of melanoma cell lines that recapitulate the phenotypic characteristics of melanomas at varying stages of malignant progression to evaluate the expression levels of Id1 in this model system and determine the mechanism of Id1 dysregulation in these tumor cells. We find elevated protein levels of Id1 to be present consistently in radial growth phase tumor cells in accordance with our primary tumor data. Id1 transcript levels were also found to be elevated in these radial growth phase melanoma cells without any appreciable evidence of gene amplification and Id1 promoter activity was found to correlate with Id expression levels. We therefore conclude that Id1 expression is primarily regulated at the transcriptional level in radial growth phase melanomas and expect that therapies that target Id1 gene expression may be useful in the treatment of Id-associated malignancies. © 2007 Wiley-Liss, Inc. [source]

Tyrosine phosphate in melanoma progression

BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2003
L. Mcardle
Summary Background Cellular tyrosine phosphorylation is regulated by two large families of enzymes. Protein tyrosine kinases (PTK) mediate addition, and protein tyrosine phosphatases (PTP), removal of phosphate from protein substrates. PTKs are oncogenes and PTPs have been hypothesized to function as tumour suppressor genes. Objectives To determine changes in tyrosine phosphate and PTP activity that occur during melanoma progression. Methods Immunohistochemistry was used to study phosphotyrosine in melanocytic lesions. In addition, PTP activity of normal melanocytes and melanoma cell lines was measured using an enzyme-linked immunosorbent assay-based system. Results Melanocytes in normal skin and most (67%) benign naevi were not immunostained. Neither were early malignant lesions (80% of malignant melanoma in situ and radial growth phase melanomas) stained. However, most advanced melanomas (100% of vertical growth phase, and 90% of metastatic melanomas) were immunoreactive. When total PTP enzyme activity was assayed in normal melanocytes and malignant melanoma cell lines, there was a significant increase in activity associated with melanoma progression. Conclusions Taken together, the data suggest increased phosphotyrosine signalling occurs during melanoma progression at the stage when cells first become competent for metastasis. [source]