TSLC1 Gene Silencing in Cervical Cancer Cell Lines and Cervical Neoplasia

Steenbergen, Renske D.M.; Kramer, Debbie; Braakhuis, Boudewijn J.M.; Stern, Peter L.; Verheijen, René H.M.; Meijer, Chris J.L.M.; Snijders, Peter J.F.

doi:10.1093/jnci/djh031

Cited by 190 publications

(189 citation statements)

References 33 publications

Supporting

Mentioning

172

Contrasting

Unclassified

Order By: Relevance

“…The detection of CADM1 promoter methylation in cervical cancer cell lines is in concordance with our previous study showing reduced CADM1 mRNA expression associated with promoter methylation in nearly all cervical cancer cell lines, and not in HPV-immortalised cells (Steenbergen et al, 2004).…”

Section: Discussionsupporting

confidence: 92%

“…Gene alterations previously detected in our in vitro model system, such as GATA-3, hTERT, MGP and CADM1, were also found in clinical samples (Steenbergen et al, 2001(Steenbergen et al, , 2002(Steenbergen et al, , 2004de Wilde et al, 2007). Therefore, we believe that the methylation events identified in the in vitro model system provide potential markers for cervical cancer detection as well, which is underlined by their large overlap with methylated gene promoters found in cervical carcinomas.…”

Section: Discussionsupporting

confidence: 62%

“…Only following immortalisation, an accumulation of methylated genes was detected, suggesting that inactivation of these genes is associated with a growth advantage of the hrHPV-containing keratinocytes. To what extent these genes (except CADM1; Steenbergen et al, 2004) are functionally involved in the different steps during the transformation process remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Anchorage-independent cell clones of FK16A and FK18B were obtained by culturing late immortal cells in soft agarose, as described previously (Steenbergen et al, 2004), resulting in the outgrowth of a limited number of colonies. Of each cell line, a single colony was isolated, referred to as FK16ASA and FK18BSA and expanded further.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Sequential gene promoter methylation during HPV-induced cervical carcinogenesis

et al. 2007

View full text Add to dashboard Cite

We aimed to link DNA methylation events occurring in cervical carcinomas to distinct stages of HPV-induced transformation. Methylation specific-multiplex ligation-dependent probe amplification (MS-MLPA) analysis of cervical carcinomas revealed promoter methylation of 12 out of 29 tumour suppressor genes analysed, with MGMT being most frequently methylated (92%). Subsequently, consecutive stages of HPV16/18-transfected keratinocytes (n ¼ 11), ranging from pre-immortal to anchorage-independent phenotypes, were analysed by MS-MLPA. Whereas no methylation was evident in pre-immortal cells, progression to anchorage independence was associated with an accumulation of frequent methylation events involving five genes, all of which were also methylated in cervical carcinomas. TP73 and ESR1 methylation became manifest in early immortal cells followed by RARb and DAPK1 methylation in late immortal passages. Complementary methylation of MGMT was related to anchorage independence. Analysis of nine cervical cancer cell lines, representing the tumorigenic phenotype, revealed in addition to these five genes frequent methylation of CADM1, CDH13 and CHFR. In conclusion, eight recurrent methylation events in cervical carcinomas could be assigned to different stages of HPV-induced transformation. Hence, our in vitro model system provides a valuable tool to further functionally address the epigenetic alterations that are common in cervical carcinomas.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Sequential gene promoter methylation during HPV-induced cervical carcinogenesis

et al. 2007

View full text Add to dashboard Cite

show abstract

“…HFKs, FK16A, FK16B, FK18A and FK18B were obtained and cultured as described before [15]. Cervical cancer cell lines SiHa, HeLa, and CaSki (American Type Culture Collection) were cultured as described previously [55]. Cell lines were authenticated using the PowerPlex 16 System (Promega) and were negative for mycoplasma.…”

Section: Methodsmentioning

confidence: 99%

Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer

et al. 2018

View full text Add to dashboard Cite

Cervical cancer development following a persistent infection with high-risk human papillomavirus (hrHPV) is driven by additional host-cell changes, such as altered DNA methylation. In previous studies, we have identified 12 methylated host genes associated with cervical cancer and pre-cancer (CIN2/3). This study systematically analyzed the onset and DNA methylation pattern of these genes during hrHPV-induced carcinogenesis using a longitudinal in vitro model of hrHPV-transformed cell lines (n = 14) and hrHPV-positive cervical scrapings (n = 113) covering various stages of cervical carcinogenesis. DNA methylation analysis was performed by quantitative methylation-specific PCR (qMSP) and relative qMSP values were used to analyze the data. The majority of genes displayed a comparable DNA methylation pattern in both cell lines and clinical specimens. DNA methylation onset occurred at early or late immortal passage, and DNA methylation levels gradually increased towards tumorigenic cells. Subsequently, we defined a so-called cancer-like methylation-high pattern based on the DNA methylation levels observed in cervical scrapings from women with cervical cancer. This cancer-like methylation-high pattern was observed in 72% (38/53) of CIN3 and 55% (11/20) of CIN2, whereas it was virtually absent in hrHPV-positive controls (1/26). In conclusion, hrHPV-induced carcinogenesis is characterized by early onset of DNA methylation, typically occurring at the pre-tumorigenic stage and with highest DNA methylation levels at the cancer stage. Host-cell DNA methylation patterns in cervical scrapings from women with CIN2 and CIN3 are heterogeneous, with a subset displaying a cancer-like methylation-high pattern, suggestive for a higher cancer risk.

show abstract