Effects of CDKN2A (p16INK4A/p14ARF) Over-Expression on Proliferation and Migration of Human Melanoma A375 Cells

Bai, Ming; Yu, Nanze; Long, Fei; Cheng, Feng; Wang, Xiaojun

doi:10.1159/000453189

Cited by 9 publications

(7 citation statements)

References 30 publications

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“…On the other hand, the highly proliferative Xiphophorus cell lines PSM and A2 exhibit only low expression of cdkn2ab mRNA and protein, whereas the slow proliferating SdSr24 cell line expresses cdkn2ab on a higher level. In vitro studies with mammalian cell lines revealed a clear inverse correlation between INK4A and/or ARF levels and proliferation (Bai et al., ) in agreement with the data from the fish cell lines. However, the expression levels of cdkn2ab determined from whole healthy organs or pigment lesion extracts are not reflecting the situation expected from the cell culture data, and thus do not provide a reliable read‐out for the proliferative state of a normal tissue or tumor.…”

Section: Discussionsupporting

confidence: 74%

“…While knockout of cdkn2ab promoted tumor progression, expression of a cdkn2ab transgene in pigment cells of the tg(mitfa:xmrk) melanoma medaka line resulted in a full suppression of tumor formation. Overexpression of p16/INK4A in A375 human melanoma cells inhibited proliferation and migration in vitro and led to decreased growth after xenotransplantation into nude mice (Bai, Yu, Long, Feng, & Wang, ). This is in agreement with our observation that cdkn2ab acts as a melanoma suppressor in fish.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of the putative tumor suppressor gene cdkn2ab in pigment cells and melanoma of Xiphophorus and medaka

Regneri

Klotz

Wilde

et al. 2018

Pigment Cell Melanoma Res

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In humans, the CDKN2A locus encodes two transcripts, INK4A and ARF. Inactivation of either one by mutations or epigenetic changes is a frequent signature of malignant melanoma and one of the most relevant entry points for melanomagenesis. To analyze whether cdkn2ab, the fish ortholog of CDKN2A, has a similar function as its human counterpart, we studied its action in fish models for human melanoma. Overexpression of cdkn2ab in a Xiphophorus melanoma cell line led to decreased proliferation and induction of a senescence-like phenotype, indicating a melanoma-suppressive function analogous to mammals. Coexpression of Xiphophorus cdkn2ab in medaka transgenic for the mitfa:xmrk melanoma-inducing gene resulted in full suppression of melanoma development, whereas CRISPR/Cas9 knockout of cdkn2ab resulted in strongly enhanced tumor growth. In summary, this provides the first functional evidence that cdkn2ab acts as a potent tumor suppressor gene in fish melanoma models.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Analysis of the putative tumor suppressor gene cdkn2ab in pigment cells and melanoma of Xiphophorus and medaka

Regneri

Klotz

Wilde

et al. 2018

Pigment Cell Melanoma Res

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“…Importantly, previous studies revealed the potential interactions between CDKN2A and PTEN genes and UVB radiation. CDKN2A may be involved in the proliferation and migration of melanoma cells, as the inhibitory effect was observed in CDKN2A -overexpressed melanoma A375 cells [ 43 ]. However, Krähn et al reported the inhibitory effect of UVB on CDKN2A expression in melanoma samples [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

UVB Radiation and Selected Tryptophan-Derived AhR Ligands—Potential Biological Interactions in Melanoma Cells

Walczak

Kazimierczak

Szalast

et al. 2021

IJMS

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Excessive UV exposure is considered the major environmental factor in melanoma progression. Human skin is constantly exposed to selected tryptophan-derived aryl hydrocarbon receptor (AhR) ligands, including kynurenine (KYN) and kynurenic acid (KYNA), as they are endogenously produced and present in various tissues and body fluids. Importantly, recent studies confirmed the biological activity of KYN and KYNA toward melanoma cells in vitro. Thus, in this study, the potential biological interactions between UVB and tryptophan metabolites KYN and KYNA were studied in melanoma A375, SK-MEL-3, and RPMI-7951 cells. It was shown that UVB enhanced the antiproliferative activity of KYN and KYNA in melanoma cells. Importantly, selected tryptophan-derived AhR ligands did not affect the invasiveness of A375 and RPMI-7951 cells; however, the stimulatory effect was observed in SK-MEL-3 cells exposed to UVB. Thus, the effect of tryptophan metabolites on metabolic activity, cell cycle regulation, and cell death in SK-MEL-3 cells exposed to UVB was assessed. In conclusion, taking into account that both UVB radiation and tryptophan-derived AhR ligands may have a crucial effect on skin cancer formation and progression, these results may have a significant impact, revealing the potential biological interactions in melanoma cells in vitro.

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“…P14ARF is one of the two proteins encoded by CDKN2A. It is involved in cell cycle regulation and senescence [ 51 ]. Its expression is decreased in melanoma compared with nevi tissues and is associated with stage, Clark grade and lymph node metastasis.…”

Section: Resultsmentioning

confidence: 99%

Bona Fide Tumor Suppressor Genes Hypermethylated in Melanoma: A Narrative Review

Güvenç

Neckebroeck

Antoranz

et al. 2021

IJMS

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Loss-of-function events in tumor suppressor genes (TSGs) contribute to the development and progression of cutaneous malignant melanoma (CMM). Epigenetic alterations are the major mechanisms of TSG inactivation, in particular, silencing by promoter CpG-island hypermethylation. TSGs are valuable tools in diagnosis and prognosis and, possibly, in future targeted therapy. The aim of this narrative review is to outline bona fide TSGs affected by promoter CpG-island hypermethylation and their functional role in the progression of CMM. We conducted a systematic literature review to identify studies providing evidence of bona fide TSGs by cell line or animal experiments. We performed a broad first search and a gene-specific second search, supplemented by reference checking. We included studies describing bona fide TSGs in CMM with promoter CpG-island hypermethylation in which inactivating mechanisms were reported. We extracted data about protein role, pathway, experiments conducted to meet the bona fide criteria and hallmarks of cancer acquired by TSG inactivation. A total of 24 studies were included, describing 24 bona fide TSGs silenced by promoter CpG-island hypermethylation in CMM. Their effect on cell proliferation, apoptosis, growth, senescence, angiogenesis, migration, invasion or metastasis is also described. These data give further insight into the role of TSGs in the progression of CMM.

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Effects of CDKN2A (p16INK4A/p14ARF) Over-Expression on Proliferation and Migration of Human Melanoma A375 Cells

Cited by 9 publications

References 30 publications

Analysis of the putative tumor suppressor gene cdkn2ab in pigment cells and melanoma of Xiphophorus and medaka

Analysis of the putative tumor suppressor gene cdkn2ab in pigment cells and melanoma of Xiphophorus and medaka

UVB Radiation and Selected Tryptophan-Derived AhR Ligands—Potential Biological Interactions in Melanoma Cells

Bona Fide Tumor Suppressor Genes Hypermethylated in Melanoma: A Narrative Review

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