Shrivastav Anuraag, Varma Shailly, Senger Arnie, Khandelwal Ramji L, Carlsen Svein, Sharma Rajendra K
Department of Pathology and Laboratory Medicine, University of Saskatchewan, Canada.
J Pathol. 2009 Jul;218(3):391-8. doi: 10.1002/path.2550.
N-myristoyltransferase (NMT) catalyses the myristoylation reaction. Since NMT activity is elevated in various cancers and activated Akt/PKB leads to cell survival, we were interested in studying if activation of Akt/PKB has any effect on NMT. Overexpression of constitutively active Akt/PKB in HepG2 cells (HepG2-CA-Akt/PKB) led to an approximately 50% reduction of NMT compared with parental HepG2 cells. Reduced NMT activity in HepG2-CA-Akt/PKB was found to be due to the NMT1 phosphorylation. We determined NMT activity in various human breast cancer cell lines with differing metastatic potentials and pseudo-normal breast cells (HBL-100). Tumourigenic or metastatic breast cancer cell lines such as MDA-MB-231, MDA-MB-435, and Hs 578T displayed reduced NMT activity. Western blot analysis revealed that NMT1 is phosphorylated in these breast cancer cells. Furthermore, patients' breast cancer tissue array revealed strong positivity and high intensity for NMT in malignant breast tissues compared with normal breast cells. A gradation in the NMT staining was observed for grade I, II, and III infiltrating ductal carcinoma breast tissues. These studies demonstrate that overexpression of Akt/PKB results in NMT1 phosphorylation and that NMT1 is phosphorylated in breast cancer cells. Immunohistochemical analysis suggests that NMT may prove to be an added diagnostic biomarker for breast cancer.
N-肉豆蔻酰转移酶（NMT）催化肉豆蔻酰化反应。由于NMT活性在多种癌症中升高，且活化的Akt/PKB可导致细胞存活，我们有兴趣研究Akt/PKB的活化是否对NMT有任何影响。在HepG2细胞（HepG2-CA-Akt/PKB）中组成型活化Akt/PKB的过表达导致与亲本HepG2细胞相比，NMT降低了约50%。发现HepG2-CA-Akt/PKB中NMT活性降低是由于NMT1磷酸化。我们测定了具有不同转移潜能的各种人乳腺癌细胞系和假正常乳腺细胞（HBL-100）中的NMT活性。致瘤性或转移性乳腺癌细胞系，如MDA-MB-231、MDA-MB-435和Hs 578T，显示出NMT活性降低。蛋白质印迹分析显示，这些乳腺癌细胞中的NMT1被磷酸化。此外，患者乳腺癌组织芯片显示，与正常乳腺细胞相比，恶性乳腺组织中NMT呈强阳性和高强度。观察到I级、II级和III级浸润性导管癌乳腺组织的NMT染色存在分级。这些研究表明，Akt/PKB的过表达导致NMT1磷酸化，且NMT1在乳腺癌细胞中被磷酸化。免疫组织化学分析表明，NMT可能被证明是乳腺癌的一种额外诊断生物标志物。
