Hailer, Amelie; Grunewald, Thomas G P; Orth, Martin; Reiss, Cora; Kneitz, Burkhard; Spahn, Martin; Butt, Elke (2014). Loss of tumor suppressor mir-203 mediates overexpression of LIM and SH3 Protein 1 (LASP1) in high-risk prostate cancer thereby increasing cell proliferation and migration. OncoTarget, 5(12), pp. 4144-4153. Impact Journals LLC
|
Text
1928-20264-5-PB.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (2MB) | Preview |
Several studies have linked overexpression of the LIM and SH3 domain protein 1 (LASP1) to progression of breast, colon, liver, and bladder cancer. However, its expression pattern and role in human prostate cancer (PCa) remained largely undefined. Analysis of published microarray data revealed a significant overexpression of LASP1 in PCa metastases compared to parental primary tumors and normal prostate epithelial cells. Subsequent gene-set enrichment analysis comparing LASP1-high and -low PCa identified an association of LASP1 with genes involved in locomotory behavior and chemokine signaling. These bioinformatic predictions were confirmed in vitro as the inducible short hairpin RNA-mediated LASP1 knockdown impaired migration and proliferation in LNCaP prostate cancer cells. By immunohistochemical staining and semi-quantitative image analysis of whole tissue sections we found an enhanced expression of LASP1 in primary PCa and lymph node metastases over benign prostatic hyperplasia. Strong cytosolic and nuclear LASP1 immunoreactivity correlated with PSA progression. Conversely, qRT-PCR analyses for mir-203, which is a known translational suppressor of LASP1 in matched RNA samples revealed an inverse correlation of LASP1 protein and mir-203 expression. Collectively, our results suggest that loss of mir-203 expression and thus uncontrolled LASP1 overexpression might drive progression of PCa.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology |
UniBE Contributor: |
Spahn, Martin |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1949-2553 |
Publisher: |
Impact Journals LLC |
Language: |
English |
Submitter: |
Katharina Morgenegg |
Date Deposited: |
26 Feb 2015 16:28 |
Last Modified: |
05 Dec 2022 14:40 |
PubMed ID: |
24980827 |
BORIS DOI: |
10.7892/boris.63457 |
URI: |
https://boris.unibe.ch/id/eprint/63457 |
Actions (login required)
 |
Edit item |