A low NM23.H1 gene expression identifying high malignancy human melanomas

Caligo, Maria A.; Grammatico, Paola; Cipollini, Giovanna; Varesco, Liliana; Porto, G. Del; Bevilacqua, Generoso

doi:10.1097/00008390-199406000-00006

Cited by 24 publications

(20 citation statements)

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“…In support of this model, low NM23-H1 expression in primary melanoma has been associated with poor outcome (6-8). The possibility is suggested that NM23-deficient metastases in melanoma and breast carcinoma may arise from an NM23-deficient and, thus, genetically unstable subpopulation within the primary tumor.…”

Section: Discussionmentioning

confidence: 77%

“…While metastasis suppressor function of nm23-h1 was validated in multiple settings (4, 5), its contribution to suppression of tumor initiation and progression is not well-understood. Low NM23 expression in primary melanomas is correlated with poor clinical outcome, however, suggesting relevance of NM23 deficiency to initiation and/or progression in earlier stages of this tumor (6-8). …”

Section: Introductionmentioning

confidence: 99%

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Metastasis Suppressor NM23-H1 Promotes Repair of UV-Induced DNA Damage and Suppresses UV-Induced Melanomagenesis

et al. 2012

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Reduced expression of the metastasis suppressor NM23-H1 is associated with aggressive forms of multiple cancers. Here, we establish that NM23-H1 (termed H1 isoform in human, M1 in mouse) and two of its attendant enzymatic activities, the 3′-5′ exonuclease and nucleoside diphosphate kinase, are novel participants in the cellular response to UV radiation (UVR)-induced DNA damage. NM23-H1 deficiency compromised the kinetics of repair for total DNA polymerase-blocking lesions and nucleotide excision repair of (6-4) photoproducts in vitro. Kinase activity of NM23-H1 was critical for rapid repair of both polychromatic UVB/UVA (290-400 nm)- and UVC (254 nm)-induced DNA damage, while its 3′-5′ exonuclease activity was dominant in the suppression of UVR-induced mutagenesis. Consistent with its role in DNA repair, NM23-H1 rapidly translocated to sites of UVR-induced (6-4) photoproduct DNA damage in the nucleus. In addition, transgenic mice hemizygous-null for nm23-m1 and nm23-m2 exhibited UVR-induced melanoma and follicular infundibular cyst formation, and tumor-associated melanocytes displayed invasion into adjacent dermis, consistent with loss of invasion-suppressing activity of NM23 in vivo. Taken together, our data demonstrate a critical role for NM23 isoforms in limiting mutagenesis and suppressing UVR-induced melanomagenesis.

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Metastasis Suppressor NM23-H1 Promotes Repair of UV-Induced DNA Damage and Suppresses UV-Induced Melanomagenesis

et al. 2012

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“…It is important to mention that in our setup, besides the particular exon, we could also identify the downstream positioned additional exons of CD44 (i.e., the expression of exon combinations if any). In the case of the WM35 human melanoma cell line, we demonstrated the expression of each variable exon (2-10), including v3 (and v6), but only v2, 4,5,7,8,9, and 10 occurred in combinations (Fig. 4, Table 4 a).…”

Section: Human Melanoma Cell Linesmentioning

confidence: 88%

“…A typical example is the expression of NM23 metastasis suppressor gene in skin MMs and their metastases. Analysis of the NM23 gene expression at the mRNA level showed decreased expression in the metastases [4,10]. However, analysis of the NM23 protein gave more controversial results [7,8,17,25,28].…”

Section: Discussionmentioning

confidence: 99%

Expression of CD44v3 splice variant is associated with the visceral metastatic phenotype of human melanoma

et al. 2001

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We analyzed the immunohistochemical expression of the metastasis-associated protein, CD44v3, in 46 primary human malignant melanomas (MMs). This is the first time that the v3 splice variant of CD44 was found to be expressed in human melanomas (15 of 46), ranging from 3% to 35% of the cell population in the positive tumors. The expression of CD44v3 was observed in tumors thicker than 1.0 mm, and one-third of these tumors proved to be positive irrespective of the thickness. Patients were followed for a minimum of 61 months. The onset of lymph node or organ metastases occurred not later than 58 months and 60 months, respectively. Of the 15 CD44v3 positive tumors, 14 were observed in the organ metastatic tumor group, comprising the majority of those cases (14 of 21), and this association proved to be statistically significant compared with the non-metastatic (P<0.05) and lymph-node metastatic cases (P<0.01). CD44v3 expression in melanoma was also confirmed at the protein and messenger (mRNA) level in several human melanoma cell lines using flow cytometry and reverse transcriptase polymerase chain reaction analysis. In parallel to CD44v3, MMP-2 expression (determined using immunohistochemistry) was significantly elevated (P<0.05) but only in the organ metastatic group of MM. The 5-year survival of patients having thicker tumors than 1.0 mm (where v3 expression occurred) who had CD44v3+ tumors was significantly lower than those of the negative ones (35.7% versus 68.2%, respectively; P=0.025). Finally, we observed that the CD44v3-expressing tumors were characterized by significantly higher MMP-2 expression than the CD44v3-negative tumors (P<0.001), indicating a possible correlation between CD44v3- and MMP-2-positive phenotype and the organ metastatic potential of MM.

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“…nm23 gene products may have different roles for different organ tumors. nm23 gene products are inversely correlated with metastatic potential and prognosis of hepatocellular carcinoma [9][10][11], breast carcinoma [12], gastric carcinoma [8,13], malignant melanoma [14,15], and adenoid cystic carcinoma [16]. In colorectal carcinoma, conflicting results have been obtained with reduced expression of nm23 either correlating with a poorer survival [17,18] or having no relationship to metastatic disease [19,20].…”

Section: Discussionmentioning

confidence: 99%

nm23-H1 protein expression in anal canal carcinoma: Does it correlate with prognosis?

et al. 2000

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The mechanisms causing enhanced nm23-H1 expression in anal canal carcinoma are unknown. Although the level and expression were not correlated with prognosis, activation of nm23-H1 gene might be a prerequisite for oncogenesis in this type of tumor, while an alternate possibility is the modification of cellular characteristics in relation to proliferation and/or differentiation as a consequence of oncogenesis.

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A low NM23.H1 gene expression identifying high malignancy human melanomas

Cited by 24 publications

References 0 publications

Metastasis Suppressor NM23-H1 Promotes Repair of UV-Induced DNA Damage and Suppresses UV-Induced Melanomagenesis

Metastasis Suppressor NM23-H1 Promotes Repair of UV-Induced DNA Damage and Suppresses UV-Induced Melanomagenesis

Expression of CD44v3 splice variant is associated with the visceral metastatic phenotype of human melanoma

nm23-H1 protein expression in anal canal carcinoma: Does it correlate with prognosis?

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