The NM23 family proteins are involved in a variety of biological processes including tumor metastasis, development, and differentiation; however, their functions in the regulation of cellular proliferation are poorly understood. We have investigated the role of one NM23 family protein, NM23H2, in the regulation of cellular proliferation directed by the extracellular signal regulated kinase (ERK) pathway. The activity of ERKs was enhanced by knockdown of endogenous NM23H2 and blocked by overexpression of NM23H2 in both NIH3T3 and HEK293 cells. Additionally, the epidermal growth factor (EGF)- and oncogenic Ras(G12R)-induced proliferation of both HEK293 and NIH3T3 cells was reduced by NM23H2 overexpression. Furthermore, activation of Raf-1, MEK and the ERKs by either EGF or Ras(G12R) was inhibited by NM23H2 overexpression. Together, our data indicate that NM23H2 is a negative regulator of cellular proliferation stimulated by EGF- and Ras-mediated activation of the ERK pathway.
Bibliographical noteFunding Information:
This work was supported by a National Research Laboratory Grant from the Korea Science and Engineering Foundation (KOSEF) funded by the Korean government (MEST) (2005-01564; 2006-02681; R112000078010020; 2007-000-10004-0). Mi-Young Lee and Woo-Jeong Jeong were supported by a BK21 scholarship from the Ministry of Education and Human Resources Development.
All Science Journal Classification (ASJC) codes
- Cancer Research