6 research outputs found
Amplified Genes May Be Overexpressed, Unchanged, or Downregulated in Cervical Cancer Cell Lines
Several copy number-altered regions (CNAs) have been identified in the genome of cervical cancer, notably, amplifications of 3q and 5p. However, the contribution of copy-number alterations to cervical carcinogenesis is unresolved because genome-wide there exists a lack of correlation between copy-number alterations and gene expression. In this study, we investigated whether CNAs in the cell lines CaLo, CaSki, HeLa, and SiHa were associated with changes in gene expression. On average, 19.2% of the cell-line genomes had CNAs. However, only 2.4% comprised minimal recurrent regions (MRRs) common to all the cell lines. Whereas 3q had limited common gains (13%), 5p was entirely duplicated recurrently. Genome-wide, only 15.6% of genes located in CNAs changed gene expression; in contrast, the rate in MRRs was up to 3 times this. Chr 5p was confirmed entirely amplified by FISH; however, maximum 33.5% of the explored genes in 5p were deregulated. In 3q, this rate was 13.4%. Even in 3q26, which had 5 MRRs and 38.7% recurrently gained SNPs, the rate was only 15.1%. Interestingly, up to 19% of deregulated genes in 5p and 73% in 3q26 were downregulated, suggesting additional factors were involved in gene repression. The deregulated genes in 3q and 5p occurred in clusters, suggesting local chromatin factors may also influence gene expression. In regions amplified discontinuously, downregulated genes increased steadily as the number of amplified SNPs increased (p<0.01, Spearman's correlation). Therefore, partial gene amplification may function in silencing gene expression. Additional genes in 1q, 3q and 5p could be involved in cervical carcinogenesis, specifically in apoptosis. These include PARP1 in 1q, TNFSF10 and ECT2 in 3q and CLPTM1L, AHRR, PDCD6, and DAP in 5p. Overall, gene expression and copy-number profiles reveal factors other than gene dosage, like epigenetic or chromatin domains, may influence gene expression within the entirely amplified genome segments
Evaluation of HIF-1α and iNOS in ischemia/reperfusion gastric model: bioimpedance, histological and immunohistochemical analyses
Gastrointestinal ischemia/reperfusion (I/R)
generates pathological alterations that could lead to
death. Early ischemic damage markers could be used to
guide therapy and improve outcomes. Aim. To relate
hypoxia-inducible factor 1α (HIF-1α) activation and
inducible nitric oxide synthase (iNOS) expression to
gastric impedance changes due to I/R damage. Methods.
Experimental animals were randomly distributed into 3
groups: control, ischemia (30 min) and I/R (60 min).
Gastric ischemia was generated by celiac artery
clamping for 30 min, and then blood flow was restored
for 60 min. Impedance spectra and biopsies of the
glandular portion were obtained for histological and
immunohistochemical analyses. Immunodetection of
both HIF-1α and iNOS was performed. Results. Under
ischemia and I/R conditions, there was an increase
(p<0.05) in the impedance parameters. Histologically,
under ischemic conditions, edema and necrosis were
observed in epithelium and significant vascular
congestion. In I/R condition, alterations of the glandular
and luminal integrity were found, which generated areas
of epithelial erosion. Immunohistochemical analysis of
HIF-1α revealed an increase (p<0.01) in the number of
immunoreactive cells in the ischemia (35.7±13.9) and
I/R (119.9±18.8) conditions compared to the control
(0.8±1.2). Immunodetection of iNOS showed an
increase (p<0.01) in the number of cells expressing
iNOS under the ischemia (5.4±2.9) and I/R conditions
(27.4±11.3) was observed compared to the control
(0.4±0.8). Conclusion. Early changes in impedance in
response to I/R is related to histopathological changes,
the nuclear stabilization and translocation of HIF-1α as
well as expression of iNOS