Martin-Caraballo Miguel
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, MD 21853, USA.
Int J Mol Sci. 2024 Apr 10;25(8):4171. doi: 10.3390/ijms25084171.
Androgen receptor signaling regulates the normal and pathological growth of the prostate. In particular, the growth and survival of prostate cancer cells is initially dependent on androgen receptor signaling. Exposure to androgen deprivation therapy leads to the development of castration-resistant prostate cancer. There is a multitude of molecular and cellular changes that occur in prostate tumor cells, including the expression of neuroendocrine features and various biomarkers, which promotes the switch of cancer cells to androgen-independent growth. These biomarkers include transcription factors (TP53, REST, BRN2, INSM1, c-Myc), signaling molecules (PTEN, Aurora kinases, retinoblastoma tumor suppressor, calcium-binding proteins), and receptors (glucocorticoid, androgen receptor-variant 7), among others. It is believed that genetic modifications, therapeutic treatments, and changes in the tumor microenvironment are contributing factors to the progression of prostate cancers with significant heterogeneity in their phenotypic characteristics. However, it is not well understood how these phenotypic characteristics and molecular modifications arise under specific treatment conditions. In this work, we summarize some of the most important molecular changes associated with the progression of prostate cancers and we describe some of the factors involved in these cellular processes.
雄激素受体信号传导调节前列腺的正常生长和病理生长。特别是，前列腺癌细胞的生长和存活最初依赖于雄激素受体信号传导。接受雄激素剥夺疗法会导致去势抵抗性前列腺癌的发展。前列腺肿瘤细胞会发生大量分子和细胞变化，包括神经内分泌特征和各种生物标志物的表达，这促进癌细胞向雄激素非依赖性生长转变。这些生物标志物包括转录因子（TP53、REST、BRN2、INSM1、c-Myc）、信号分子（PTEN、极光激酶、视网膜母细胞瘤肿瘤抑制因子、钙结合蛋白）和受体（糖皮质激素、雄激素受体变体7）等。据信，基因修饰、治疗方法以及肿瘤微环境的变化是导致前列腺癌进展的因素，这些前列腺癌在表型特征上具有显著的异质性。然而，目前尚不清楚这些表型特征和分子修饰在特定治疗条件下是如何产生的。在这项工作中，我们总结了一些与前列腺癌进展相关的最重要的分子变化，并描述了这些细胞过程中涉及的一些因素。
