Securin (hPTTG1) expression is regulated by beta-catenin/TCF in human colorectal carcinoma.
Overexpression of the transcriptional activator beta-catenin, mostly owing to loss-of-function mutations of the adenomatous polyposis coli (APC) tumour suppressor gene, is crucial for the initiation and progression of human colorectal carcinogenesis. Securin is a regulator of chromosome separation and its overexpression has been shown to be involved in different tumour-promoting processes, like transformation, hyperproliferation and angiogenesis, and correlates with tumour cell invasion. However, the molecular mechanism leading to securin overexpression in human colorectal cancer is unknown. Here we show a correlated high expression of beta-catenin and securin (hPTTG1) in colorectal adenomas and carcinomas and further demonstrate that securin is a target of beta-catenin transcriptional activation. This implies that deregulation of the beta-catenin/T-cell factor-signalling pathway leads to overexpression of securin in human colorectal cancer, which subsequently may contribute to tumour progression.
Hlubek
F
F
Department of Pathology, Ludwig-Maximilians University of Munich, Thalkirchner Str. 36, 80337 Munich, Germany. Falk.Hlubek@med.uni-muenchen.de
Pfeiffer
S
S
Budczies
J
J
Spaderna
S
S
Jung
A
A
Kirchner
T
T
Brabletz
T
T
D000230:Adenocarcinoma / Q000235:genetics* / Q000601:surgery; D001665:Binding Sites; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000601:surgery; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D009363:Neoplasm Proteins / Q000097:blood* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064249:Securin; D051820:TCF Transcription Factors / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D017931:DNA Primers; D009363:Neoplasm Proteins; D064249:Securin; D051820:TCF Transcription Factors; D051176:beta Catenin; C578002:pituitary tumor-transforming protein 1, human