7 research outputs found
Identification of a Proliferation Gene Cluster Associated with HPV E6/E7 Expression Level and Viral DNA Load in Invasive Cervical Carcinoma
Specific HPV DNA sequences are associated with more than 90% of invasive
carcinomas of the uterine cervix. Viral E6 and E7 oncogenes are key mediators
in cell transformation by disrupting TP53 and RB pathways. To investigate
molecular mechanisms involved in the progression of invasive cervical
carcinoma, we performed a gene expression study on cases selected according to
viral and clinical parameters. Using Coupled Two-Way Clustering and Sorting
Points Into Neighbourhoods methods, we identified a Cervical Cancer
Proliferation Cluster composed of 163 highly correlated transcripts, many of
which corresponded to E2F pathway genes controlling cell proliferation, whereas
no primary TP53 targets were present in this cluster. The average expression
level of the genes of this cluster was higher in tumours with an early relapse
than in tumours with a favourable course (P=0.026). Moreover, we found that
E6/E7 mRNA expression level was positively correlated with the expression level
of the cluster genes and with viral DNA load. These findings suggest that HPV
E6/E7 expression level plays a key role in the progression of invasive
carcinoma of the uterine cervix via the deregulation of cellular genes
controlling tumour cell proliferation. HPV expression level may thus correspond
to a biological marker useful for prognosis assessment and specific therapy of
the disease
Coiling Instability of Multilamellar Membrane Tubes with Anchored Polymers
We study experimentally a coiling instability of cylindrical multilamellar
stacks of phospholipid membranes, induced by polymers with hydrophobic anchors
grafted along their hydrophilic backbone. Our system is unique in that coils
form in the absence of both twist and adhesion. We interpret our experimental
results in terms of a model in which local membrane curvature and polymer
concentration are coupled. The model predicts the occurrence of maximally tight
coils above a threshold polymer occupancy. A proper comparison between the
model and experiment involved imaging of projections from simulated coiled
tubes with maximal curvature and complicated torsions.Comment: 11 pages + 7 GIF figures + 10 JPEG figure
Relationship of gene expression and chromosomal abnormalities in colorectal cancer. Cancer Res
Several studies have verified the existence of multiple chromosomal abnormalities in colon cancer. However, the relationships between DNA copy number and gene expression have not been adequately explored nor globally monitored during the progression of the disease. In this work, three types of array-generated data (expression, single nucleotide polymorphism, and comparative genomic hybridization) were collected from a large set of colon cancer patients at various stages of the disease. Probes were annotated to specific chromosomal locations and coordinated alterations in DNA copy number and transcription levels were revealed at specific positions. We show that across many large regions of the genome, changes in expression level are correlated with alterations in DNA content. Often, large chromosomal segments