Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-2-16
pubmed:abstractText
Dysregulation of the centrosome complex and chromosomal segregation has been associated with aneuploid cells and aggressive solid tumours, but the relevance of this mechanism to the adenoma-carcinoma sequence of sporadic colorectal cancer (sCRC), especially tumours showing chromosomal instability (CIN), is still unknown. In a series of matching normal epithelial cells (n = 41), dysplastic cells (n = 18), and invasive carcinoma cells (n = 41) from cases with sCRC, mRNA levels of the centrosomal kinase Aurora-A/STK15 and the chromosomal passenger- and cell cycle-associated molecules Incenp, Survivin, Mad-2, and Cyclin-D1 were therefore measured with specific reference to the type of genetic instability. Compared with normal epithelium, significant up-regulation of mRNAs was already present for Aurora-A/STK15 (p = 0.0313) in dysplastic cells and for all investigated markers in invasive carcinoma. Whereas Aurora-A/STK15 mRNA levels were similarly up-regulated in dysplastic and invasive carcinoma cells (p = 0.0797), Survivin (p = 0.0046) and Cyclin-D1 (p = 0.0017) mRNA levels increased from dysplastic to invasive carcinoma cells. In carcinomas, Incenp mRNA correlated with T category (p = 0.0149), and Survivin (p = 0.0382) and Cyclin-D1 (p = 0.0185) were associated with tumour differentiation. Importantly, a significantly higher (p = 0.0419) fold-change of Aurora-A/STK15 mRNA (p = 0.0419), but not Incenp, Survivin, Mad-2 or Cyclin-D1, was observed in sCRC cases with CIN (n = 29) when compared with tumours showing microsatellite instability (MIN, n = 10). The present data are the first to show an early increase of the centrosomal kinase Aurora-A/STK15 in the adenoma-carcinoma sequence of sCRC. The regulation of this kinase differs in CIN- and MIN-type sCRCs and the pattern of changes is different from those of the cell-cycle-associated markers Survivin, Mad-2, and Cyclin-D1. This reinforces the concept of preferential dysregulation of the centrosome complex in CIN-type (aneuploid), compared with MIN-type, sporadic colorectal cancers and may influence the response to and efficiency of novel therapeutics targeting Aurora kinases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/BIRC5 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Chromosomal Proteins, Non-Histone, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1, http://linkedlifedata.com/resource/pubmed/chemical/Genetic Markers, http://linkedlifedata.com/resource/pubmed/chemical/INCENP protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins, http://linkedlifedata.com/resource/pubmed/chemical/MAD2L1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/aurora kinase
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3417
pubmed:author
pubmed:issnType
Print
pubmed:volume
208
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
462-72
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16402339-Adenoma, pubmed-meshheading:16402339-Adult, pubmed-meshheading:16402339-Aneuploidy, pubmed-meshheading:16402339-Calcium-Binding Proteins, pubmed-meshheading:16402339-Carcinoma, pubmed-meshheading:16402339-Case-Control Studies, pubmed-meshheading:16402339-Cell Cycle, pubmed-meshheading:16402339-Cell Cycle Proteins, pubmed-meshheading:16402339-Centrosome, pubmed-meshheading:16402339-Chromosomal Proteins, Non-Histone, pubmed-meshheading:16402339-Colorectal Neoplasms, pubmed-meshheading:16402339-Cyclin D1, pubmed-meshheading:16402339-Disease Progression, pubmed-meshheading:16402339-Epithelial Cells, pubmed-meshheading:16402339-Female, pubmed-meshheading:16402339-Gene Expression Regulation, Neoplastic, pubmed-meshheading:16402339-Genetic Markers, pubmed-meshheading:16402339-Humans, pubmed-meshheading:16402339-Immunohistochemistry, pubmed-meshheading:16402339-Inhibitor of Apoptosis Proteins, pubmed-meshheading:16402339-Male, pubmed-meshheading:16402339-Microsatellite Repeats, pubmed-meshheading:16402339-Microtubule-Associated Proteins, pubmed-meshheading:16402339-Neoplasm Proteins, pubmed-meshheading:16402339-Precancerous Conditions, pubmed-meshheading:16402339-Protein-Serine-Threonine Kinases, pubmed-meshheading:16402339-RNA, Messenger, pubmed-meshheading:16402339-Repressor Proteins, pubmed-meshheading:16402339-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16402339-Statistics, Nonparametric
pubmed:year
2006
pubmed:articleTitle
Centrosome-, chromosomal-passenger- and cell-cycle-associated mRNAs are differentially regulated in the development of sporadic colorectal cancer.
pubmed:affiliation
Pathologisches Institut, Universitätsklinikum, Freiburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't