Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Genetic and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
J Cell Physiol. 2020 Jul;235(7-8):5835-5846. doi: 10.1002/jcp.29523. Epub 2020 Jan 22.
Breast cancer (BC) is an important cause of female cancer-related death. It has recently been demonstrated that metabolic disorders including lipid metabolism are a hallmark of cancer cells. Lipin-1 is an enzyme that displays phosphatidate phosphatase activity and regulates the rate-limiting step in the pathway of triglycerides and phospholipids synthesis. The objective of this study was to evaluate lipin-1 expression, its prognostic significance, and its correlation with p53 tumor suppressor in patients with BC. In this study, 55 pairs of fresh samples of BC and adjacent noncancerous tissue were used to analyze lipin-1, using quantitative real-time polymerase chain reaction and immunohistochemistry (IHC) staining. The expression of other clinicopathological variables and p53 was also examined using IHC technique. The cell migration was studied in MCF-7 and MDA-MB231 cells following the inhibition of lipin-1 by propranolol. Our results show that the relative expression of lipin-1 messenger RNA was significantly higher in BC tissues compared with the adjacent normal tissue and its inhibition reduced cell migration in cancer cells. This upregulation was negatively correlated with histological grade of tumor and p53 status (p = .001 and p = .034) respectively and positively correlated with the tumor size (p = .006). Our results also seem to indicate that the high lipin-1 expression is related to a good prognosis in patients with BC. The expression of lipin-1 may be considered as a novel independent prognostic factor. The inhibition of lipin-1 may also have therapeutic significance for patients with BC. The correlation between lipin-1 and p53 confirms the role of p53 in the regulation of lipid metabolism in cancer cells.
乳腺癌（BC）是女性癌症相关死亡的重要原因。最近已经证明，包括脂质代谢在内的代谢紊乱是癌细胞的一个标志。脂磷酶 1 是一种具有磷酸二酯酶活性的酶，调节甘油三酯和磷脂合成途径中的限速步骤。本研究的目的是评估脂磷酶 1 在 BC 患者中的表达、其预后意义及其与 p53 肿瘤抑制因子的相关性。在这项研究中，使用定量实时聚合酶链反应和免疫组织化学（IHC）染色分析了 55 对 BC 和相邻非癌组织的脂磷酶 1。还使用 IHC 技术检查了其他临床病理变量和 p53 的表达。在 MCF-7 和 MDA-MB231 细胞中，通过普萘洛尔抑制脂磷酶 1 来研究细胞迁移。我们的结果表明，与相邻正常组织相比，BC 组织中脂磷酶 1 信使 RNA 的相对表达显著升高，其抑制降低了癌细胞的细胞迁移。这种上调与肿瘤的组织学分级和 p53 状态呈负相关（p = 0.001 和 p = 0.034），与肿瘤大小呈正相关（p = 0.006）。我们的结果似乎还表明，BC 患者中高脂磷酶 1 表达与良好的预后相关。脂磷酶 1 的表达可以被认为是一个新的独立的预后因素。脂磷酶 1 的抑制也可能对 BC 患者具有治疗意义。脂磷酶 1 与 p53 之间的相关性证实了 p53 在调节癌细胞脂质代谢中的作用。
