Article
Reduced metastasis-suppressor gene mRNA expression in brain metastases
Reduzierte mRNA-Expression von Metastasen-Suppressor-Genen in Hirnmetastasen
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Published: | April 23, 2004 |
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Outline
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Objective
Brain metastasis is a challenging condition in cancer. The molecular mechanism remains largely unknown. The Metastasis Suppressor Genes (MSG) nm23, KiSS1, KAI1, BRMS1 and Mkk4 have been associated with the metastatic potential of human cancers in vitro and in vivo. The aim of this study was to estimate MSG expression in brain metastases.
Methods
Fresh frozen tissue samples were obtained intraoperatively from patients with breast, colorectal and non-small cell lung cancer (NSCLC) brain metastasis. After total RNA-isolation, semi-quantative RT-PCR was performed using specific primers for nm23, KiSS1, KAI1, BRMS1 and Mkk4. Actin was used as internal standard. After agarose-gel-electrophoresis, expression was estimated determining the appearance of the band as well as determining the intensity of the bands with PC-BAS computer program.
Results
In breast cancer brain metastases, all 5 genes showed decreased expression in comparison to primary tumors, although to a variable degree. Overall decreased expression was noted for Kai1, BRMS1 and Mkk4. Colorectal cancer brain metastases showed decreased expression for Nm23, Kai1, BRMS and Mkk4 when compared to primaries. However, only Mkk4 expression was clearly decreased in all metastases examined. KiSS1 expression was comparable in metastatic and primary lesions. In contrast to breast and colorectal cancer specimens, NSCLC brain metastases showed variable expression values lacking clear trends when compared to primary tumors. Finally, estimation of band intensity reveled roughly the same expression trends.
Conclusions
The results of this screening procedure suggest a potential role for Kai1, BRMS1 and Mkk4 in the pathogenesis of breast cancer brain metastasis. BRMS1 and Mkk4 expression was also decreased in colorectal cancer brain lesions. In contrast, results in NSCLC specimens were contradictory and lacking clear trends.