EXPRESSION OF BONE MORPHOGENETIC PROTEIN MESSENGER-RNAS BY NORMAL RAT AND HUMAN PROSTATE AND PROSTATE-CANCER CELLS

EXPRESSION OF BONE MORPHOGENETIC PROTEIN MESSENGER-RNAS BY NORMAL RAT AND HUMAN PROSTATE AND PROSTATE-CANCER CELLS
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DOI:
10.1002/pros.2990240406
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发表时间:
1994-04-01
期刊:
影响因子:
2.8
通讯作者:
MUNDY, GR
MUNDY, GR
中科院分区:
医学3区
文献类型:
--
作者:
HARRIS, SE;HARRIS, MA;MUNDY, GR

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已知人前列腺癌细胞产生几种生长调节因子,包括转化生长因子β(TGF β)和肝素结合成纤维细胞生长因子(FGF),其可能在前列腺形态发生以及前列腺癌细胞行为中发挥尚未确定的作用。最近,已经鉴定了在扩展的TGF β家族中的蛋白质家族,骨形态发生蛋白(BMP),其在体内刺激骨形成,并且其中,所述蛋白质可能参与胚胎发生期间的多种形态发生过程。这些强大的形态发生因子能够重新定向肌肉间充质细胞,使其沿着骨组织的线条分化。我们研究了一些特征良好的大鼠和人前列腺癌细胞系的BMP 2,3,4和6信使RNA的表达。从正常人和大鼠腹侧前列腺、大鼠前列腺腺癌PAIII肿瘤及其衍生的培养细胞以及人前列腺癌细胞系PC-3、LNCaP和DU-145中分离聚(A +)-RNA。使用BMP 2、3、4和Vgr-1(BMP 6)cDNA探针测量BMP mRNA水平。正常和肿瘤性前列腺组织都表达这些BMP mRNA,尽管表达水平因肿瘤而异。正常人前列腺主要表达BMP 4 mRNA,人前列腺癌PC-3和DU-145也是如此。PC-3也大量表达BMP-2 mRNA和BMP-3 mRNA。正常大鼠腹侧前列腺表达所有这些BMP mRNA,但大鼠前列腺癌PA III主要表达BMP 3 mRNA。这些正常和肿瘤细胞以不同的量表达不同的BMP的原因尚不清楚。然而,如果这些BMP以生物活性形式表达,则它们可能对正常前列腺生长和形态发生、对肿瘤性前列腺细胞行为产生重要影响,甚至可能有助于前列腺癌细胞刺激骨中转移性肿瘤部位的新骨形成的能力。(C)1994 Wiley-Liss,Inc.
Human prostate cancer cells are known to produce several growth regulatory factors, including transforming growth factor beta (TGF beta) and heparin-binding fibroblast growth factors (FGFs), which may play as-yet-undefined roles in prostate gland morphogenesis, as well as in prostate cancer cell behavior. Recently, a family of proteins in the extended TGF beta family, the bone morphogenetic proteins (BMPs), has been identified which stimulates bone formation in vivo, and in which, the proteins are likely involved in a variety of morphogenetic processes during embryogenesis. These powerful morphogenetic factors are capable of redirecting muscle mesenchyme cells to differentiate along the lines of bone tissue. We examined a number of well-characterized rat and human prostate cancer cell lines for the expression of BMP 2, 3, 4, and 6 messenger RNA. Poly(A +)-RNA was isolated from normal human and rat ventral prostate, from the rat prostate adenocarcinoma PAIII tumor and cultured cells derived from it, and from human prostate cancer cell lines PC-3, LNCaP, and DU-145. BMP mRNA levels were measured using BMP 2, 3, 4 and Vgr-1 (BMP 6) cDNA probes. Both normal and neoplastic prostate tissue expressed these BMP mRNAs, although the level of expression varied from tumor to tumor. Normal human prostate expressed BMP 4 mRNA predominantly, as did the human prostate cancers PC-3 and DU-145. PC-3 also expressed BMP 2 mRNA and BMP 3 mRNA in large amounts. Normal rat ventral prostate expressed all these BMP mRNAs, but the rat prostate adenocarcinoma PAIII expressed predominantly BMP 3 mRNA. The reason that different BMPs are expressed in varying amounts by these normal and neoplastic cells is unknown. However, if these BMPs are expressed in biologically active form, they could be responsible for important effects on normal prostate growth and morphogenesis, on neoplastic prostate cell behavior, and could even contribute to the capacity of prostatic cancer cells to stimulate new bone formation at metastatic tumor sites in bone. (C) 1994 Wiley-Liss, Inc.