TMPRSS2:ERG gene fusion expression regulates bone markers and enhances the osteoblastic phenotype of prostate cancer bone metastases.
Cancer Lett
; 438: 32-43, 2018 12 01.
Article
in En
| MEDLINE
| ID: mdl-30201302
ABSTRACT
Prostate cancers have a strong propensity to metastasize to bone and promote osteoblastic lesions. TMPRSS2ERG is the most frequent gene rearrangement identified in prostate cancer, but whether it is involved in prostate cancer bone metastases is largely unknown. We exploited an intratibial metastasis model to address this issue and we found that ectopic expression of the TMPRSS2ERG fusion enhances the ability of prostate cancer cell lines to induce osteoblastic lesions by stimulating bone formation and inhibiting the osteolytic response. In line with these in vivo results, we demonstrate that the TMPRSS2ERG fusion protein increases the expression of osteoblastic markers, including Collagen Type I Alpha 1 Chain and Alkaline Phosphatase, as well as Endothelin-1, a protein with a documented role in osteoblastic bone lesion formation. Moreover, we determined that the TMPRSS2ERG fusion protein is bound to the regulatory regions of these genes in prostate cancer cell lines, and we report that the expression levels of these osteoblastic markers are correlated with the expression of the TMPRSS2ERG fusion in patient metastasis samples. Taken together, our results reveal that the TMPRSS2ERG gene fusion is involved in osteoblastic lesion formation induced by prostate cancer cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteoblasts
/
Prostatic Neoplasms
/
Bone Neoplasms
/
Biomarkers, Tumor
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Gene Expression Regulation, Neoplastic
/
Oncogene Proteins, Fusion
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cancer Lett
Year:
2018
Type:
Article
Affiliation country:
Canada