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Overexpression of Akt/PKB modulates N‐myristoyltransferase activity in cancer cells
Author(s) -
Shrivastav Anuraag,
Varma Shailly,
Senger Arnie,
Khandelwal Ramji L,
Carlsen Svein,
Sharma Rajendra K
Publication year - 2009
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2550
Subject(s) - protein kinase b , breast cancer , cancer research , phosphorylation , cancer , western blot , mcf 7 , cancer cell , pi3k/akt/mtor pathway , chemistry , biology , medicine , signal transduction , microbiology and biotechnology , biochemistry , human breast , gene
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. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.