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Down-regulation of Lsm1 is involved in human prostate cancer progression
S Takahashi1, S Suzuki, S Inaguma
1First Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. sattak@med.nagoya-cu.ac.jp
Abstract:
Elucidation of genetic alterations is an approach to understanding the underlying molecular mechanisms of progression of human prostate cancers. We have searched for genes differentially expressed in advanced prostate cancers using cDNA-representational difference analysis, and thereby isolated the Lsm1 as one of down-regulated gene. An Lsm1 expression vector was transfected into PC3 cells, normally featuring down-regulated Lsm1, and four transfectants were established. No differences in morphology or cell proliferation were evident in comparison with parent PC3 or PC3/mock-transfectants. In contrast, significant suppression of invasive potential or metastatic ability of Lsm1 transfectants was observed in the Matrigel chemoinvasion assay and in nude mice, respectively. With human prostate cancers, almost all of informative prostatectomised cases without neoadjuvant therapy showed allelic retention in the Lsm1 region, whereas refractory cancers frequently showed allelic loss in this region. No critical gene mutations were found in open reading frame of Lsm1 in prostate cancers examined by PCR-SSCP analysis, including localised and refractory cancers. These results suggest that Lsm1 is deeply involved in prostate cancer progression through its down-regulation, independent of any gene mutation.
Insights
The Lsm1 gene is down-regulated in advanced prostate cancers, suppressing tumor invasion and metastasis. This down-regulation, not gene mutation, drives prostate cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Understanding genetic alterations is key to deciphering prostate cancer progression.
- Identifying differentially expressed genes in advanced prostate cancers aids in uncovering molecular mechanisms.
Purpose of the Study:
- To investigate the role of Lsm1 in prostate cancer progression.
- To determine if Lsm1 down-regulation impacts tumor invasiveness and metastatic potential.
Main Methods:
- cDNA-representational difference analysis to identify differentially expressed genes.
- Lsm1 gene transfection into PC3 prostate cancer cells.
- Matrigel chemoinvasion assays and in vivo studies in nude mice.
- Analysis of Lsm1 allelic status and gene mutations in human prostate cancer tissues.
Main Results:
- Lsm1 was identified as a down-regulated gene in advanced prostate cancers.
- Restoration of Lsm1 expression in PC3 cells significantly suppressed invasion and metastasis.
- Allelic loss of Lsm1 was frequent in refractory prostate cancers, while retention was observed in non-refractory cases.
- No critical mutations were found in the Lsm1 open reading frame.
Conclusions:
- Lsm1 down-regulation plays a significant role in prostate cancer progression.
- The suppressive effects on invasion and metastasis are independent of Lsm1 gene mutations.
- Lsm1 is a potential therapeutic target for inhibiting prostate cancer spread.