Abstract | BACKGROUND:
Cyclin A1 is a cell cycle regulator that has been implicated in the progression of prostate cancer. Its role in invasion and metastasis of this disease has not been characterized. METHODS: RESULTS:
Cyclin A1 protein and mRNA expression were statistically significantly higher in prostate cancers than in adjacent benign tissues. A statistically significant correlation between expression of cyclin A1 and of MMP2, MMP9, and VEGF was observed in prostate tumors from 482 patients (P values from Spearman rank correlation tests < .001). PC3 cells that overexpressed cyclin A1 showed increased invasiveness, and inhibition of cyclin A1 expression via shRNA expression reduced invasiveness of these cells. Eight of 10 mice (80%) bearing PC3 cells overexpressing cyclin A1 had infiltration of tumor cells in lymph node, liver, and lung, but all 10 mice bearing tumors expressing control vector were free of liver and lung metastases and only one mouse from this group had lymph node metastasis (P values from Fisher exact tests < .001). Cyclin A1, in concert with AR, bound to and increased expression from the VEGF and MMP2 promoters. CONCLUSIONS:
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Authors | Barbara Wegiel, Anders Bjartell, Johanna Tuomela, Nishtman Dizeyi, Martina Tinzl, Leszek Helczynski, Elise Nilsson, Leo E Otterbein, Pirkko Härkönen, Jenny Liao Persson |
Journal | Journal of the National Cancer Institute
(J Natl Cancer Inst)
Vol. 100
Issue 14
Pg. 1022-36
(Jul 16 2008)
ISSN: 1460-2105 [Electronic] United States |
PMID | 18612129
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers, Tumor
- CCNA1 protein, human
- Cyclin A
- Cyclin A1
- RNA, Messenger
- Receptors, Androgen
- Vascular Endothelial Growth Factor A
- Metribolone
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
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Topics |
- Aged
- Aged, 80 and over
- Animals
- Biomarkers, Tumor
(metabolism)
- Chromatin Immunoprecipitation
- Cyclin A
(genetics, metabolism)
- Cyclin A1
- Enzyme-Linked Immunosorbent Assay
- Gene Expression Regulation, Neoplastic
- Humans
- Immunoblotting
- Immunohistochemistry
- Male
- Matrix Metalloproteinase 2
(metabolism)
- Matrix Metalloproteinase 9
(metabolism)
- Metribolone
(pharmacology)
- Mice
- Neoplasm Invasiveness
- Neovascularization, Pathologic
(metabolism)
- Oligonucleotide Array Sequence Analysis
- Prostatic Neoplasms
(blood supply, metabolism, pathology)
- RNA, Messenger
(metabolism)
- Receptors, Androgen
(metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- Up-Regulation
- Vascular Endothelial Growth Factor A
(metabolism)
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