Proto-Oncogene Proteins

Publication Title: 
Oncogene

Replicative senescence is thought to be a significant barrier to human tumorigenesis, which in human fibroblasts, and many other cell types, can be overcome experimentally by combined loss of function of p53 and Rb 'pathways'. To avoid the confounding pleiotropic effects of HPVE7 frequently used in such studies, here we have employed retroviral vectors over-expressing CDK4 or CDK6 as a more representative model of naturally-occurring mutations targeting the Rb pathway.

Author(s): 
Morris, Mark
Hepburn, Peter
Wynford-Thomas, David
Publication Title: 
Cancer Research

The vast majority of breast cancers are carcinomas that arise from mammary epithelial cells (MECs). One of the key early events in tumorigenic transformation is the ability of cells to overcome replicative senescence. However, the precise genetic changes that are responsible for this event in MECs is largely unknown. Here, we report that Bmi-1, originally identified as a c-Myc cooperating oncoprotein, can bypass senescence, extend the replicative life span, and immortalize MECs. Furthermore, Bmi-1 was overexpressed in immortal MECs and several breast cancer cell lines.

Author(s): 
Dimri, Goberdhan P.
Martinez, Jose-Luis
Jacobs, Jacqueline J. L.
Keblusek, Petra
Itahana, Koji
Van Lohuizen, Maarten
Campisi, Judith
Wazer, David E.
Band, Vimla
Publication Title: 
Aging Cell

Fetal cardiomyocytes have been proposed as a potential source of cell-based therapy for heart failure. This study examined cellular senescence in cultured human fetal ventricular cardiomyocytes (HFCs). HFCs were isolated and identified by immunocytochemistry and RT-PCR. Cells were found to senesce after 20-25 population doublings, as determined by growth arrest, morphological changes and senescence-associated beta-galactosidase activity. Using the telomeric repeat amplification protocol assay, telomerase activity was undetectable in primary HFCs.

Author(s): 
Ball, Andrew J.
Levine, Fred
Publication Title: 
Experimental Cell Research

Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood.

Author(s): 
Becerikli, Mustafa
Jacobsen, Frank
Rittig, Andrea
Kˆhne, Wiebke
Nambiar, Sandeep
Mirmohammadsadegh, Alireza
Stricker, Ingo
Tannapfel, Andrea
Wieczorek, Stefan
Epplen, Joerg Thomas
Tilkorn, Daniel
Steinstraesser, Lars
Publication Title: 
Mammalian Genome: Official Journal of the International Mammalian Genome Society

Prader-Willi syndrome (PWS) results from loss of function of a 1.0- to 1.5-Mb domain of imprinted, paternally expressed genes in human Chromosome (Chr) 15q11-q13. The loss of imprinted gene expression in the homologous region in mouse Chr 7C leads to a similar neonatal PWS phenotype. Several protein-coding genes in the human PWS region are intronless, possibly arising by retrotransposition. Here we present evidence for continued acquisition of genes by the mouse PWS region during evolution.

Author(s): 
Chai, J. H.
Locke, D. P.
Ohta, T.
Greally, J. M.
Nicholls, R. D.
Publication Title: 
Translational Psychiatry

Increasing evidence suggests that epigenetic dysfunction may account for the alteration of gene transcription present in neuropsychiatric disorders such as schizophrenia (SZ), bipolar disorder (BP) and autism.

Author(s): 
Dong, E.
Gavin, D. P.
Chen, Y.
Davis, J.
Publication Title: 
Schizophrenia Research

The epigenetic dysregulation of the brain genome associated with the clinical manifestations of schizophrenia (SZ) includes altered DNA promoter methylation of several candidate genes. We and others have reported that two enzymes that belong to the DNA-methylation/demethylation network pathways-DNMT1 (DNA-methyltransferase) and ten-eleven translocator-1(TET1) methylcytosine deoxygenase are abnormally increased in corticolimbic structures of SZ postmortem brain.

Author(s): 
Auta, J.
Smith, R. C.
Dong, E.
Tueting, P.
Sershen, H.
Boules, S.
Lajtha, A.
Davis, J.
Guidotti, A.
Publication Title: 
Translational Psychiatry

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by symptoms related to altered social interactions/communication and restricted and repetitive behaviors. In addition to genetic risk, epigenetic mechanisms (which include DNA methylation/demethylation) are thought to be important in the etiopathogenesis of ASD.

Author(s): 
Zhubi, A.
Chen, Y.
Dong, E.
Cook, E. H.
Guidotti, A.
Grayson, D. R.
Publication Title: 
Anticancer Research

Artemisinin (AR) is a widely used antimalarial drug. Recently, additional uses for AR as an anticancer drug were discovered. Using TUNEL, immunohistochemistry (IHS) markers and flow cytometry techniques, we evaluated the effect of AR and 5-FU on HPV 16 immortalized and transformed human gingival epithelial (IHGK) cells. The results of TUNEL showed that AR-treated IHGK cells consisted of 82% positive cells, while 5-FU-treated cells consisted of 18% positive cells.

Author(s): 
Yamachika, Eiki
Habte, Temesgen
Oda, Dolphine
Publication Title: 
Cancer Research

Withaferin A (WA) is derived from the medicinal plant Withania somnifera, which has been safely used for centuries in Indian Ayurvedic medicine for treatment of different ailments. We now show, for the first time, that WA exhibits significant activity against human breast cancer cells in culture and in vivo. The WA treatment decreased viability of MCF-7 (estrogen-responsive) and MDA-MB-231 (estrogen-independent) human breast cancer cells in a concentration-dependent manner.

Author(s): 
Stan, Silvia D.
Hahm, Eun-Ryeong
Warin, Renaud
Singh, Shivendra V.

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