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Bone morphogenetic protin (BMP) and their receptors in prostate cancer.

前列腺癌中的骨形态发生蛋白（BMP）及其受体。

基本信息

批准号：
10671484
负责人：
TAKEHARA Toshiyuki
金额：
$ 1.98万
依托单位：
Miyazaki Medical College Gant-in-Aid for Scientific Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671484/
关键词：
Prostate cancer BMP MPR Bone metastasis Androgen 前立腺癌

项目摘要

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-b (TGF-b) family and have been identified as factors which stimulate bone formation in vivo. They turned out to be multifunctional molecules regulating the growth, differentiation and apoptosis in various target cells. Some BMPs and their receptors (BMPRs) are expressed on prostate cancer cells. We have previously reported that BMPR-IB mRNA expression is highest in the prostate, a characteristic which is not shared by the other BMPRs, BMPR-IA and -II.However, the amounts of BMPR-IB mRNA were significantly low in prostate tissues after androgen withdrawal therapy. They were also low in prostate cancer cell lines. Semi-quantitative RT-PCR showed that BMPR-IB mRNA was induced by androgen in the androgen-sensitive human prostatic cancer cell line LNCaP, while the expression of BMPR-IA and -II mRNAs was not affected by androgen. When the recombinant human BMP-2 was added to the LNCaP cells in the presence of androgen, the cell growth was inhibited. In contrast, the growth rate was increased by addition of the same ligand, when the cells were cultured in the absence of androgen ; under this condition, the amounts of BMPR-IB mRNA were significantly decreased. These observations showed that the amounts of BMPR-IB, but not those of BMPR-IA were regulated by androgen and further suggest that BMPR-IA and BMPR-IB differentially modulate prostate cancer cell growth in response to BMP under different hormonal conditions ; BMPR-IA elicits growth stimulation and BMPR-IB conveys negative regulatory signal in response to BMP-2. We also examined the chromosome localization of BMPR-IA and -IB gene.By in situ hybridization and radiation hybrid mapping, we showed that the assignment of the BMPR-IA and BMPR-IB genes to human chromosome 10q22.3 and 4q23-q24.

骨形态发生蛋白（BMPs）属于转化生长因子-b（TGF-b）家族，并且已被鉴定为体内刺激骨形成的因子。它们是调节多种靶细胞生长、分化和凋亡的多功能分子。一些BMP及其受体（BMPRs）在前列腺癌细胞上表达。我们以前曾报道，BMPR-IB mRNA的表达是最高的前列腺，这是不共享的其他BMPRs，BMPR-IA和-II的特征。然而，BMPR-IB mRNA的量显着降低雄激素戒断治疗后的前列腺组织。它们在前列腺癌细胞系中也很低。半定量RT-PCR结果显示，BMPR-IB mRNA在雄激素敏感的人前列腺癌细胞系LNCaP中的表达受雄激素的诱导，而BMPR-IA和-II mRNA的表达不受雄激素的影响。当重组人BMP-2在雄激素存在下加入LNCaP细胞时，细胞生长受到抑制。相反，当细胞在不存在雄激素的情况下培养时，通过添加相同的配体来增加生长速率;在这种条件下，BMPR-IB mRNA的量显著降低。这些观察结果表明，BMPR-IB的量而不是BMPR-IA的量受雄激素调节，并进一步表明BMPR-IA和BMPR-IB在不同激素条件下响应于BMP差异性地调节前列腺癌细胞生长; BMPR-IA增强生长刺激，BMPR-IB响应于BMP-2传递负调节信号。通过原位杂交和辐射杂交定位，我们发现BMPR-IA和BMPR-IB基因定位于人类染色体10q22.3和4 q23-q24。