18 research outputs found
The selective continued linkage of centromeres from mitosis to interphase in the absence of mammalian separase
Separase is an evolutionarily conserved protease that is essential for chromosome segregation and cleaves cohesin Scc1/Rad21, which joins the sister chromatids together. Although mammalian separase also functions in chromosome segregation, our understanding of this process in mammals is still incomplete. We generated separase knockout mice, reporting an essential function for mammalian separase. Separase-deficient mouse embryonic fibroblasts exhibited severely restrained increases in cell number, polyploid chromosomes, and amplified centrosomes. Chromosome spreads demonstrated that multiple chromosomes connected to a centromeric region. Live observation demonstrated that the chromosomes of separase-deficient cells condensed, but failed to segregate, although subsequent cytokinesis and chromosome decondensation proceeded normally. These results establish that mammalian separase is essential for the separation of centromeres, but not of the arm regions of chromosomes. Other cell cycle events, such as mitotic exit, DNA replication, and centrosome duplication appear to occur normally. We also demonstrated that heterozygous separase-deficient cells exhibited severely restrained increases in cell number with apparently normal mitosis in the absence of securin, which is an inhibitory partner of separase
18. asırda "Hırkai şerif" ziyareti
Taha Toros Arşivi, Dosya No: 120-Saraylar. Not: Gazetenin "Tarihten Sahifeler" köşesinde yayımlanmıştır.İstanbul Kalkınma Ajansı (TR10/14/YEN/0033) İstanbul Development Agency (TR10/14/YEN/0033
Hexokinase 2 in colorectal cancer: a potent prognostic factor associated with glycolysis, proliferation and migration
Background. It is well known that
proliferating carcinoma cells preferentially use aerobic
glycolysis rather than oxidative phosphorylation for
energy production. Hexokinase 2 (HK2) plays a pivotal
role in the glycolytic pathway. Previous studies have
demonstrated that HK2 activity is markedly increased in
various malignant neoplasms, but the clinical and
biological significance of HK2 remain largely unclear in
the colorectal carcinoma.
Patients and methods. We performed immunohistochemistry for HK2 in 195 colorectal carcinoma tissues.
We also used HCT8 and HT29 colon carcinoma cells in
in vitro studies.
Results. HK2 immunoreactivity was detected in 100
out of 195 (51%) colorectal carcinoma tissues, and the
immunohistochemical HK2 status was significantly
associated with tumor size, depth of invasion, liver
metastasis and TNM stage in these cases. Moreover, the
HK2 status was significantly associated with increased
incidence of recurrence and overall mortality of the
patients, and multivariate analyses demonstrated that
HK2 status was an independent prognostic factor for
both disease-free and overall survival. Subsequent in
vitro experiments revealed that both HCT8 and HT29
colon carcinoma cells transfected with specific siRNA
for HK2 significantly decreased the lactate production,
proliferation activity and migration property.
Conclusion. These results suggest that HK2 plays
important roles in the glycolytic, proliferation and
migration properties of colorectal carcinoma and,
therefore, HK2 status is a potent worse prognostic factor
in colorectal cancer patient