Cutaneous Malignant Melanoma

Cummins, Deborah L.; Cummins, Jordan M.; Pantle, Hardin; Silverman, Michael A.; Leonard, Aimee L.; Chanmugam, Arjun

doi:10.4065/81.4.500

Cited by 283 publications

(230 citation statements)

References 77 publications

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“…When diagnosed early, melanoma may be cured by surgical resection. However, metastatic malignant melanoma is largely refractory to existing therapies and has a very poor prognosis, with a median survival rate of six months and a five-year survival rate of <5% (16).…”

Section: Discussionmentioning

confidence: 99%

Optimization and establishment of RNA interference-mediated knockdown of the progestagen-associated endometrial protein gene in human metastatic melanoma cell lines

Chai¹,

Qiao²,

Wang³

et al. 2013

Molecular Medicine Reports

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Abstract. Progestagen-associated endometrial protein (PAEP), also termed glycodelin, is a 28-kDa glycoprotein of the lipocalin superfamily that is expressed in a variety of tumors, including gynecological tumors, lung cancer and melanoma. To determine the biological functions of the PAEP gene in tumor development and progression, the production of transient and stable PAEP knockdown cell models is required. In the present study, RNA interference technology was used to silence PAEP gene expression in melanoma and transfection was screened for and the conditions were optimized using fluorescence microscopy, flow cytometry, qPCR and western blot analysis. The results of the present study showed that the transient transfection of melanoma cells with 100 nmol/l PAEP siRNA or lentiviral PAEP small hairpin RNA (shRNA) [multiplicity of infection (MOI), 100 pfu/cell] efficiently knocked down target gene expression. To establish stable PAEP knockdown cell lines, melanoma cells were infected with a low MOI (10 pfu/cell) of lentiviral particles expressing PAEP shRNA. Following puromycin screening, the PAEP gene knockdown efficiency was demonstrated to be >80% in 624-Mel and 624.38-Mel cell lines, which was validated by western blot analysis. Therefore, melanoma cell lines with stable knockdown of PAEP were successfully established and may be used as effective cell models to study the biological functions of the PAEP gene in melanoma.

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Section: Discussionmentioning

confidence: 99%

Optimization and establishment of RNA interference-mediated knockdown of the progestagen-associated endometrial protein gene in human metastatic melanoma cell lines

Chai¹,

Qiao²,

Wang³

et al. 2013

Molecular Medicine Reports

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“…Queensland, Australia has the highest incidence of melanoma in the world, with 34,000 residents in a population of $4 million people being diagnosed with the disease in the last two decades (Coory et al, 2006). The 5-year survival rate for metastatic malignant melanoma is less than 5% as the tumors are largely refractory to existing therapies (Cummins et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Identification of candidate tumor suppressor genes inactivated by promoter methylation in melanoma

Bonazzi

Irwin

Hayward

2008

Genes Chromosomes & Cancer

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Tumor suppressor genes (TSGs) are sometimes inactivated by transcriptional silencing through promoter hypermethylation. To identify novel methylated TSGs in melanoma, we carried out global mRNA expression profiling on a panel of 12 melanoma cell lines treated with a combination of 5-Aza-2-deoxycytidine (5AzadC) and an inhibitor of histone deacetylase, Trichostatin A. Reactivation of gene expression after drug treatment was assessed using Illumina whole-genome microarrays. After qRT-PCR confirmation, we followed up 8 genes (AKAP12, ARHGEF16, ARHGAP27, ENC1, PPP1R3C, PPP1R14C, RARRES1, and TP53INP1) by quantitative DNA methylation analysis using mass spectrometry of base-specific cleaved amplification products in panels of melanoma cell lines and fresh tumors. PPP1R3C, ENC1, RARRES1, and TP53INP1, showed reduced mRNA expression in 35-59% of the melanoma cell lines compared to melanocytes and which was correlated with a high proportion of promoter methylation (>40-60%). The same genes also showed extensive promoter methylation in 6-25% of the tumor samples, thus confirming them as novel candidate TSGs in melanoma.

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“…For years, emphasis has been placed on the increasing time trends of incidence and mortality rates of cutaneous malignant melanoma (CMM) (3,4) and, in contrast, on the protective role of vitamin D regarding many types of internal cancer and other diseases (5)(6)(7). Too much sun exposure has been blamed for the high and increasing incidence rates of CMM.…”

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confidence: 99%

Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure

Moan

Porojnicu

Dahlback

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

206

147

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Solar radiation is the main cause of skin cancers. However, it also is a main source of vitamin D for humans. Because the optimal status of vitamin D protects against internal cancers and a number of other diseases, a controversy exists: Will increased sun exposure lead to net health benefits or risks? We calculated the relative yield of vitamin D photosynthesis as a function of latitude with a radiative transfer model and cylinder geometry for the human skin surface. The annual yield of vitamin D is 3.4 and 4.8 times larger below the equator than in the U.K. and Scandinavia, respectively. In populations with similar skin types, there are clear latitude gradients of all major forms of skin cancer, indicating a northsouth gradient in real sun exposure. Surprisingly, the incidence rates of major internal cancers also increase from north to south. However, the survival prognosis also improves significantly from north to south. Reasons for these findings are discussed in view of the role of vitamin D. In Norway, melanoma rates increased by a factor of 6 from 1960 to 1990, while the prognosis improved in the same period. After 1990, melanoma rates have remained constant or even decreased in age groups <50 years, whereas the prognosis has not improved further. These data, together with those for internal cancers and the beneficial effects of an optimal vitamin D status, indicate that increased sun exposure may lead to improved cancer prognosis and, possibly, give more positive than adverse health effects.body mass index ͉ cutaneous malignant melanoma ͉ squamous cell carcinoma ͉ ultraviolet radiation T here is a controversy as to whether increased sun exposure to Western populations would prolong or shorten lifetime expectancy, result in fewer or more cancer deaths, and, in general, lead to health benefits or risks (1, 2). For years, emphasis has been placed on the increasing time trends of incidence and mortality rates of cutaneous malignant melanoma (CMM) (3, 4) and, in contrast, on the protective role of vitamin D regarding many types of internal cancer and other diseases (5-7). Too much sun exposure has been blamed for the high and increasing incidence rates of CMM. However, solar radiation is a major, if not the main, source of vitamin D in humans. Therefore, a population's increased sun exposure leads to improved vitamin D status. The observation that the incidence and mortality of several types of internal cancers decreases with decreasing latitude in the United States and other countries initiated the research on vitamin D-cancer relationships in the 1980s and 1990s. However, in some cases, there is an inverse gradient of the rates of internal cancer with latitude (1), with the rates being higher in regions with high annual UV fluences (New Zealand and Australia) than in countries with low annual UV fluences (Northern Europe, Scandinavia, and the U.K.), despite the fact that the populations of these regions are closely related genetically or, at least, have similar skin types, which is important for the photosy...

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Cutaneous Malignant Melanoma

Cited by 283 publications

References 77 publications

Optimization and establishment of RNA interference-mediated knockdown of the progestagen-associated endometrial protein gene in human metastatic melanoma cell lines

Optimization and establishment of RNA interference-mediated knockdown of the progestagen-associated endometrial protein gene in human metastatic melanoma cell lines

Identification of candidate tumor suppressor genes inactivated by promoter methylation in melanoma

Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure

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