Analysis of 14-3-3σ expression in hyperproliferative skin diseases reveals selective loss associated with CpG-methylation in basal cell carcinoma

Lodygin, Dimitri; Yazdi, Amir S.; Sander, Christian; Herzinger, Thomas; Hermeking, Heiko

doi:10.1038/sj.onc.1206854

Cited by 80 publications

(80 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…34,35 However, again no correlation was found between the p63 status and 14-3-3s expression in hyperproliferative skin disease. 20 These studies all suggest independence of 14-3-3s expression of p53 and its homologues p63 and p73.…”

Section: Discussionmentioning

confidence: 87%

“…Including our series, epigenetic transcriptional silencing of 14-3-3s has been demonstrated in malignancies from prostate, endometrium, ovary, breast, lung, liver, skin, stomach and oral squamous cell carcinoma. [15][16][17][18]20,21,[24][25][26] Another recent immunohistochemical study has shown loss of 14-3-3s expression in prostate cancer. 27 By preselecting areas of highest Gleason score in their tumor biopsies and by using a different 14-3-3s antibody, these authors find low or absent levels of 14-3-3s in an even higher percentage of tumors.…”

Section: Discussionmentioning

confidence: 99%

“…20,24 However, in contrast to most malignancies, gene expression profiling as well as tissue microarray screens have recently demonstrated overexpression of 14-3-3s in pancreatic ductal adenocarcinomas and biliary cancers. 28,29 Interestingly, deregulated overexpression of 14-3-3s was associated with CpG island hypomethylation.…”

Section: Discussionmentioning

confidence: 99%

“…15 For each PCR reaction, three controls were included: in addition to a water control (negative), two DNA samples of breast cancer cell lines (MDA-MB-435, MCF-7) were analyzed known to result in strong signals for the methylated and unmethylated alleles, respectively (MCF-7, MDA-MB-435). 15,20 14-3-3r Methylation and Messenger RNA Expression upon 5-Azacytidine Treatment Nine urological and gynecological cancer cell lines (all from the American Tissue Culture Collection (ATCC) cultivated according to the supplier's recommendations) were analyzed for 14-3-3s promoter methylation by PCR (as describe above). Two cancer cell lines (AN3CA, LNCAP) with strong 14-3-3s CpG methylation were further analyzed for 14-3-3s expression at the messenger RNA (mRNA) level before and after blocking cellular methylation by 5-azacytidine (5-Aza, SIGMA Biochemicals, Buchs, Switzerland) treatment as described previously.…”

Section: Methylation-specific Pcrmentioning

confidence: 99%

“…Following studies demonstrated epigenetic silencing of 14-3-3s expression in gastric, liver, lung, cervical, oral squamous cell carcinoma, and basal cell carcinoma of the skin. [16][17][18][19][20][21] The aims of this study were: first, to study the expression of 14-3-3s by using immunohistochemistry on a multiple tumor tissue microarrays containing a large number of urological and gynecological cancers. Second, to explore the relation between 14-3-3s expression and p53 using the D07 and the PAB240 clone recognizing wild-type and mutated p53 isoforms respectively.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Downregulation of 14-3-3σ in ovary, prostate and endometrial carcinomas is associated with CpG island methylation

et al. 2005

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methylation-specific Pcrmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Downregulation of 14-3-3σ in ovary, prostate and endometrial carcinomas is associated with CpG island methylation

et al. 2005

Self Cite

View full text Add to dashboard Cite

Gene expression and methylation status of 14‐3‐3σ in human renal carcinoma tissues

Liang

Shen

et al. 2008

IUBMB Life

View full text Add to dashboard Cite

Loss of 14‐3‐3σ expression mainly by methylation‐mediated silencing has been reported in several human cancers, but the methylation status of 14‐3‐3σ in human renal carcinoma is rarely studied so far. In this report, 14‐3‐3σ expression was first examined by RT‐PCR and immunohistochemistry, and further we investigated the methylation status by methylation‐specific PCR and the correlation between 14‐3‐3σ expression and its methylation. We found 14‐3‐3σ expression was lost in 27 of 31 renal tissues including 16 renal carcinoma tissues, eight para‐cancerous kidney tissues and seven normal kidney tissues. Among 16 renal carcinoma tissues, 14 cases had complete hypermethylation of 14‐3‐3σ. Eight para‐cancerous kidney tissues were almost completely methylated except one case had both methylation and unmethylation. Among seven normal kidney tissues, five cases had partial methylation, and the other two cases were completely methylated. In addition, 14‐3‐3σ mRNA had weak expression in OS‐RC‐2 cells, but it increased with gradual demethylation after treatment by a demethylation agent, 5‐aza‐2′‐deoxycytidine. In general, 14‐3‐3σ mRNA was mostly unexpressed, and its DNA frequently hypermethylated within 14‐3‐3σ coding region was closely associated with the gene silencing in cancerous and para‐cancerous kidney tissues. 14‐3‐3σ was also frequently methylated and almost silencing in normal kidney tissues. However, the methylation frequency was gradually reinforced with the extent of malignancy from normal to para‐cancerous and cancerous kidney tissues. © 2008 IUBMB IUBMB Life, 60(8): 534–540, 2008

show abstract

14‐3‐3σ/Stratifin and p21 limit AKT‐related malignant progression in skin carcinogenesis following MDM2‐associated p53 loss

McMenemy,

Guo,

Quinn

et al. 2024

Molecular Carcinogenesis

View full text Add to dashboard Cite

To study mechanisms driving/inhibiting skin carcinogenesis, stage‐specific expression of 14‐3‐3σ (Stratifin) was analyzed in skin carcinogenesis driven by activated rasHa/fos expression (HK1.ras/fos) and ablation of PTEN‐mediated AKT regulation (K14.creP/Δ5PTENflx/flx). Consistent with 14‐3‐3σ roles in epidermal differentiation, HK1.ras hyperplasia and papillomas displayed elevated 14‐3‐3σ expression in supra‐basal keratinocytes, paralleled by supra‐basal p‐MDM2166 activation and sporadic p‐AKT473 expression. In bi‐genic HK1.fos/Δ5PTENflx/flx hyperplasia, basal‐layer 14‐3‐3σ expression appeared, and alongside p53/p21, was associated with keratinocyte differentiation and keratoacanthoma etiology. Tri‐genic HK1.ras/fos‐Δ5PTENflx/flx hyperplasia/papillomas initially displayed increased basal‐layer 14‐3‐3σ, suggesting attempts to maintain supra‐basal p‐MDM2166 and protect basal‐layer p53. However, HK1.ras/fos‐Δ5PTENflx/flx papillomas exhibited increasing basal‐layer p‐MDM2166 activation that reduced p53, which coincided with malignant conversion. Despite p53 loss, 14‐3‐3σ expression persisted in well‐differentiated squamous cell carcinomas (wdSCCs) and alongside elevated p21, limited malignant progression via inhibiting p‐AKT1473 expression; until 14‐3‐3σ/p21 loss facilitated progression to aggressive SCC exhibiting uniform p‐AKT1473. Analysis of TPA‐promoted HK1.ras‐Δ5PTENflx/flx mouse skin, demonstrated early loss of 14‐3‐3σ/p53/p21 in hyperplasia and papillomas, with increased p‐MDM2166/p‐AKT1473 that resulted in rapid malignant conversion and progression to poorly differentiated SCC. In 2D/3D cultures, membranous 14‐3‐3σ expression observed in normal HaCaT and SP1ras61 papilloma keratinocytes was unexpectedly detected in malignant T52ras61/v‐fos SCC cells cultured in monolayers, but not invasive 3D‐cells. Collectively, these data suggest 14‐3‐3σ/Stratifin exerts suppressive roles in papillomatogenesis via MDM2/p53‐dependent mechanisms; while persistent p53‐independent expression in early wdSCC may involve p21‐mediated AKT1 inhibition to limit malignant progression.

show abstract

Analysis of 14-3-3σ expression in hyperproliferative skin diseases reveals selective loss associated with CpG-methylation in basal cell carcinoma

Cited by 80 publications

References 17 publications

Downregulation of 14-3-3σ in ovary, prostate and endometrial carcinomas is associated with CpG island methylation

Downregulation of 14-3-3σ in ovary, prostate and endometrial carcinomas is associated with CpG island methylation

Gene expression and methylation status of 14‐3‐3σ in human renal carcinoma tissues

14‐3‐3σ/Stratifin and p21 limit AKT‐related malignant progression in skin carcinogenesis following MDM2‐associated p53 loss

Contact Info

Product

Resources

About