The &lt;i&gt;TP53&lt;/i&gt; Tumor Suppressor Gene and Melanoma Tumorigenesis: Is There a Relationship?

Hussein, Mahmoud R.

doi:10.1159/000081103

Cited by 26 publications

(20 citation statements)

References 57 publications

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“…These findings are in line with those reported in the literature. 40 Our results showed that the number of securin-and p53-positive cells are significantly correlated, and that in some melanomas, overexpression of both proteins occurred in the same neoplastic cells. Although we have no firm in vitro data, we can speculate that, in analogy with other cancers, hPTTG1 overexpression in melanoma modulates the transcriptional activity of p53, resulting in impairment of apoptosis.…”

Section: Discussionsupporting

confidence: 51%

Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma

et al. 2006

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Human pituitary tumour-transforming gene 1 or hPTTG1 is a proto-oncogene that codes for securin, a protein involved in sister chromatid separation. Based on previous microarray data, we studied the expression of hPTTG1/securin in melanocytic lesions. In contrast to nevi and radial growth phase melanomas, securin was expressed by scattered cells in the vertical growth phase, suggesting a role in tumour progression. In a series of 29 nodular and 29 superficial spreading melanomas, matched for all histological prognostic parameters, securin expression was significantly correlated with the nodular subtype (P ¼ 0.018) and not related to thickness. In other cancers, hPTTG1 is involved in various oncogenic pathways, including induction of neovascularisation and aneuploidy, and inhibition of p53 activity. We found coexpression of securin with wildtype p53 in the same neoplastic cells in a minority of melanomas. Expression of securin was significantly correlated with the extent of aneuploidy but not with basic fibroblast growth factor immunoreactivity or microvessel density. DNA cytometry revealed that nuclei-overexpressing securin frequently showed tetraploidy or aneuploidy. Our data show that hPTTG1 is frequently overexpressed in nodular melanoma, and suggest that hPTTG1 may act as an oncogene in the vertical growth phase, either by inhibiting anaphase, thereby causing aneuploidy and genomic instability, or by modulating the function of p53, thereby impairing apoptosis.

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Section: Discussionsupporting

confidence: 51%

Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma

et al. 2006

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“…p53 expression in melanocytic skin lesions varies considerably in different studies from a small percentage of positively stained cells (57) to Ͼ50% of tumor cells (58,59). However, different studies support the notion that p53 alterations may play a role in later stages of melanoma development and progression (60,61).…”

Section: Discussionmentioning

confidence: 99%

Recognition of Fresh Human Tumor by Human Peripheral Blood Lymphocytes Transduced with a Bicistronic Retroviral Vector Encoding a Murine Anti-p53 TCR

Cohen

Zheng

Bray

et al. 2005

The Journal of Immunology

115

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The p53 protein is markedly up-regulated in a high proportion of human malignancies. Using an HLA-A2 transgenic mouse model, it was possible to isolate high-avidity murine CTLs that recognize class I-restricted human p53 epitopes. We isolated the α- and β-chain of a TCR from a highly avid murine CTL clone that recognized the human p53264–272 epitope. These genes were cloned into a retroviral vector that mediated high efficiency gene transfer into primary human lymphocytes. Efficiencies of >90% for gene transfer into lymphocytes were obtained without selection for transduced cells. The p53 TCR-transduced lymphocytes were able to specifically recognize with high-avidity, peptide-pulsed APCs as well as HLA-A2.1+ cells transfected with either wild-type or mutant p53 protein. p53 TCR-transduced cells demonstrated recognition and killing of a broad spectrum of human tumor cell lines as well as recognition of fresh human tumor cells. Interestingly, both CD8+ and CD4+ subsets were capable of recognizing and killing target cells, stressing the potential application of such a CD8-independent TCR molecule that can mediate both helper and cytotoxic responses. These results suggest that lymphocytes genetically engineered to express anti-p53 TCR may be of value for the adoptive immunotherapy of patients with a variety of common malignancies.

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“…However, the role of p53 in regulation of IGF-1R seems to be more complex and probably also involves post-transcriptional mechanisms (Girnita et al, 2000;Lee et al, 2003). This can be exemplified by malignant melanoma cells, most often harbouring wild-type p53 (Hussein, 2004), which exhibit overexpression of IGF-1R. Upon inhibition of wild-type p53 in these cells, they surprisingly responded with a drastic IGF-1R downregulation and cell death (Girnita et al, 2000).…”

Section: Interactions Between Igf-1r and Oncogenesmentioning

confidence: 99%

Role of insulin-like growth factor 1 receptor signalling in cancer

2005

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The insulin-like growth factor (IGF-1) signalling is highly implicated in cancer. In this signalling the IGF-1 receptor (IGF-1R) is unquestionable, the predominating single factor. IGF-1R is crucial for tumour transformation and survival of malignant cell, but is only partially involved in normal cell growth. This is in part due to the interactions with oncogenes. Recent findings suggest a close interplay with the p53/MDM2 pathway. Disturbances in components in the p53/MDM2/IGF-1R network may cause IGF-1R upregulation and growth advantage for the cancer cell. Targeting of IGF-1R is more and more seen as a promising option for future cancer therapy. Single chain antibodies and small molecules with selective effects on IGF-1R dependent malignant growth are of particular interest. Forthcoming clinical trials are welcome and will indeed be the only way to evaluate the impact of IGF-1R targeting in human cancer.

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The <i>TP53</i> Tumor Suppressor Gene and Melanoma Tumorigenesis: Is There a Relationship?

Cited by 26 publications

References 57 publications

Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma

Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma

Recognition of Fresh Human Tumor by Human Peripheral Blood Lymphocytes Transduced with a Bicistronic Retroviral Vector Encoding a Murine Anti-p53 TCR

Role of insulin-like growth factor 1 receptor signalling in cancer

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