Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Cells. 2022 Jul 9;11(14):2155. doi: 10.3390/cells11142155.
Approximately 90% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). PDAC is the fourth leading cause of cancer death world-wide. Therapies for PDAC are largely ineffective due to the dense desmoplastic tumor microenvironment which prevents chemotherapeutic drugs and small molecule inhibitors from exerting effective anti-cancer effects. In this review, we will discuss the roles of TP53 and miRs on the PDAC tumor microenvironment and how loss of the normal functions of TP53 promote tumor progression. The gene is mutated in approximately 50% of pancreatic cancers. Often, these TP53 mutations are point mutations which confer additional functions for the TP53 proteins. These are called gain of function (GOF) mutations (mut). Another class of TP53 mutations are deletions which result in loss of the TP53 protein; these are referred to TP53-null mutations. We have organized this review into various components/properties of the PDAC microenvironment and how they may be altered in the presence of mutant TP53 and loss of certain miR expression.
大约 90%的胰腺癌是胰腺导管腺癌（PDAC）。PDAC 是全球第四大癌症死亡原因。由于致密的纤维瘤性肿瘤微环境，化疗药物和小分子抑制剂无法发挥有效的抗癌作用，PDAC 的治疗方法在很大程度上是无效的。在这篇综述中，我们将讨论 TP53 和 miRs 在 PDAC 肿瘤微环境中的作用，以及正常 TP53 功能的丧失如何促进肿瘤的进展。该基因在大约 50%的胰腺癌中发生突变。通常，这些 TP53 突变是点突变，赋予 TP53 蛋白额外的功能。这些突变被称为功能获得（GOF）突变（mut）。另一类 TP53 突变是缺失导致 TP53 蛋白丢失；这些突变被称为 TP53 缺失突变。我们将这篇综述组织成 PDAC 微环境的各个组成部分/特性，以及在存在突变型 TP53 和某些 miR 表达缺失的情况下，它们可能会发生怎样的改变。
