Camparo Philippe, Vieillefond Annick
Laboratoire d'anatomie et cytologie pathologiques, Hôpital d'Instruction des Armées Val-de-Grâce, 74 boulevard de Port-Royal, 75005 Paris.
Bull Cancer. 2007 Jul;94(7 Suppl):F77-88.
A meta-analysis of recent data from the literature underscores the considerable body of present knowledge concerning prostate carcinogenesis, in part due to the numerous molecular biology tools now at our disposal. As concerns early events, much interest is being paid to modifications in the expression of GSTP1 and NKX3.1 occurring in totipotent stem cell populations. The discovery of fusion genes implicating TMPRSS2 and ERG (and, on rare occasions, other ETS family transcription factors) constitutes a major advance. Under physiological androgenic stimulation, the presence of these fusion genes leads to overexpression of genes involved in cell growth and differentiation. Concomitantly, alterations in numerous signalling pathways (growth factors, Wnt-beta catenine, PI3K/Akt) are responsible for the onset of an aggressive tumor phenotype. Hormono-independence is currently explained by an amplification of, or mutations in, androgenic receptors. These are facilitated by genomic instabilities linked to alterations in proteins which regulate gene expression, such as EZH2, and by the influence of the tumor microenvironment. Disturbances in the interactions between tumor cells and the microenvironment contribute to local extension of the tumor. Changes in the expression of E-cadherin are responsible for modifications in cell adhesion to the extracellular matrix. The expression of metalloproteases and of angiogenic factors favors tumor dissemination. Finally, the bone tropism in prostate metastases is probably linked to osteomimetic properties of prostate tumor cells which are capable of expressing certain proteins involved in bone remodelling, such as Runx-2, BSP (bone sialoprotein) and BMP (bone morphogenetic protein). Numerous studies remain to be carried out in order to correlate the identified genetic profiles and molecular anomalies with tumor prognosis. Nevertheless, the possibility of decrypting these anomalies for use in therapeutic applications is encouraging.
对近期文献数据的一项荟萃分析强调了目前关于前列腺癌发生的大量知识，部分原因是我们现在有众多分子生物学工具可用。关于早期事件，人们对全能干细胞群体中GSTP1和NKX3.1表达的改变非常感兴趣。涉及TMPRSS2和ERG（以及极少数情况下的其他ETS家族转录因子）的融合基因的发现是一项重大进展。在生理雄激素刺激下，这些融合基因的存在导致参与细胞生长和分化的基因过度表达。同时，众多信号通路（生长因子、Wnt-β连环蛋白、PI3K/Akt）的改变导致侵袭性肿瘤表型的出现。目前，激素非依赖性是由雄激素受体的扩增或突变来解释的。与调节基因表达的蛋白质（如EZH2）改变相关的基因组不稳定性以及肿瘤微环境的影响促进了这种情况。肿瘤细胞与微环境之间相互作用的紊乱导致肿瘤的局部扩展。E-钙黏蛋白表达的变化导致细胞与细胞外基质黏附的改变。金属蛋白酶和血管生成因子的表达有利于肿瘤扩散。最后，前列腺转移中的骨嗜性可能与前列腺肿瘤细胞的骨模拟特性有关，这些细胞能够表达某些参与骨重塑的蛋白质，如Runx-2、骨唾液蛋白（BSP）和骨形态发生蛋白（BMP）。为了将已确定的基因谱和分子异常与肿瘤预后相关联，仍有许多研究有待开展。然而，解密这些异常以用于治疗应用的可能性令人鼓舞。
