Persistent human papillomavirus infections cause infected epithelial cells to lose cellular polarity leading to cell transformation. Glycolipid-enriched membrane (GEM) rafts are implicated in polarized sorting of apical membrane proteins in epithelial cells and even in signal transduction. The MAL and BENE are essential component of the GEM raft's machinery for apical sorting of membrane proteins. In this study we demonstrated down-regulation of MAL and BENE mRNA in over two-thirds of primary cervical squamous cell cancers (14 and 15 of 20 cases, for MAL and BENE, respectively) when compared to corresponding non-cancerous uterine squamous cells. Allelic loss or hyper-methylation was not accompanied by MAL or BENE mRNA down-expression in human primary cervical cancers in microsatellite allelic analysis and HpaII-PCR-based methylation analysis of the MAL and BENE genomic region. In addition, we note down-regulation of these genes in established cervical cancer cell lines. These results suggest that down-regulation of MAL and BENE genes, which are essential components of the cellular polarized sorting system, play an important role in human cervical squamous cell cancer development.
At 16 weeks' gestation, ultrasonography demonstrated a band-like structure in the amniotic cavity of a 27-year-old woman. Color Doppler imaging revealed blood flow in this band-like structure and a diagnosis of a placenta with succenturiate lobe rather than an amniotic band was made.
We have established two distinct human cervical cell lines, NCC16 and NCE16, after traiisfecting human papillomavirus type 16 (HPV16) DNA into normal human ecto‐cervical and endo‐cervical epithelial cells, respectively. Both lines expressed HPV16 E6 and E7 as detected hy reverse transcriptase‐polymerase chain reaction and northern Wot hybridization. These cells have been passaged for over 100 population doublings and express strong telomerase activity. Neither cell line was tumorigenic in athymic nu/nu mice. However, both NCC16 and NCE16 developed abnormally stratified architectures following implantation with a silicon membrane sheet in the back of athymic nude mice. The former cells were pathohistologically similar to carcinoma, while the latter produced Alcian‐blue positive cells, suggesting the occurrence of metaplastic changes. These distinct cell lines offer a useful model system for the study of cervical carcinogenesis and of its regulatory mechanism after HPV infection in different regions of the uterine cervix.
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