Alteration of gene expression in response to bone morphogenetic protein-2 in androgen-dependent human prostate cancer LNCaP cells
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Updated: Aug 13, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Toru Kumagai1, Kentaro Tomari, Takahisa Shimizu
1Department of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.
Abstract:
Bone morphogenetic protein (BMP)-2, a multifunctional member of the transforming growth factor (TGF)-beta superfamily with powerful osteoinductive effects, has various biological activities in a variety of cells. We observed that BMP-2 inhibits cell proliferation in the androgen-dependent human prostate cancer cell line, LNCaP. To investigate the mechanism of inhibition of androgen-dependent growth by BMP-2, we compared the gene expression in LNCaP cells treated with dihydrotestosterone (DHT) to that of LNCaP cells treated with DHT and BMP-2, using DNA microarray analysis. Of 8,400 human genes on the gene chip, 38 genes were up-regulated by >2.0-fold and 48 genes were down-regulated by <0.5-fold by treatment with BMP-2. These genes were involved in a variety of cellular functions, including signal transduction, transcription regulation, enzymes, transporters, structural molecules and translation. RT-PCR analysis showed that CH1CL and BMX were up-regulated and DACH1 and WNT5A were down-regulated by treatment with BMP-2. Furthermore, we detected an increase of WNT5A protein in the medium by DHT and inhibition of the increase by BMP-2. In the present study, we identified several BMP-2-responsive genes in LNCaP cells. Further studies of the roles of these genes may clarify the mechanisms underlying the inhibition of cell proliferation by BMP-2 and identify better approaches for the prevention and treatment of prostate cancer.
Insights
Bone morphogenetic protein (BMP)-2 inhibits prostate cancer cell growth. This study identified specific genes regulated by BMP-2, offering potential new strategies for prostate cancer prevention and treatment.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Bone morphogenetic protein (BMP)-2, a TGF-beta superfamily member, exhibits potent osteoinductive properties.
- BMP-2 demonstrates inhibitory effects on cell proliferation in the LNCaP human prostate cancer cell line.
Purpose of the Study:
- To elucidate the molecular mechanisms by which BMP-2 inhibits androgen-dependent prostate cancer growth.
- To identify genes regulated by BMP-2 in LNCaP cells using DNA microarray analysis.
Main Methods:
- DNA microarray analysis was employed to compare gene expression profiles in LNCaP cells treated with dihydrotestosterone (DHT) versus DHT plus BMP-2.
- Reverse transcription polymerase chain reaction (RT-PCR) was used to validate the expression changes of specific genes.
- Western blot analysis or ELISA was used to detect protein level changes, specifically WNT5A.
Main Results:
- BMP-2 treatment altered the expression of numerous genes, with 38 genes upregulated (>2.0-fold) and 48 genes downregulated (<0.5-fold) out of 8,400 analyzed.
- RT-PCR confirmed upregulation of CH1CL and BMX, and downregulation of DACH1 and WNT5A by BMP-2.
- DHT increased WNT5A protein levels, an effect inhibited by BMP-2.
Conclusions:
- This study identified several BMP-2-responsive genes in prostate cancer cells.
- Understanding the function of these identified genes may reveal novel mechanisms of BMP-2-mediated growth inhibition.
- These findings could lead to improved approaches for prostate cancer prevention and therapy.
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