Moreover, proliferation was also reduced in the stathmin1 siRNA group these (Supplementary Figure 2). In contrast, apoptosis was significantly increased in the stathmin1 siRNA group compared with the SCR group (Supplementary Figure 3). Figure 7 Effect of stathmin1 silencing on in vivo tumour growth. (A) SNU638 cells were transfected with scrambled (SCR) small interfering RNA (siRNA) or stathmin1 (STMN1) siRNA, and nude mice were inoculated subcutaneously with 2 �� 106 cells at two sites … Discussion Stathmin1 is expressed in the more poorly differentiated types of several cancer tissues. In prostate cancer, stathmin1 expression is similar in Gleason patterns 3 and 4; however, a significant increase in stathmin1 levels occurs in Gleason pattern 5.

Similarly, greater expression of stathmin1 was observed in androgen-independent cancer cells than in androgen-dependent cancer cells (Friedrich et al, 1995). In breast cancer, stathmin1 levels negatively correlated with estrogen receptor expression and positively correlated with a high fraction of aneuploid cells, proliferation, tumour size and histopathological grade (Brattsand, 2000). In this study, we characterised stathmin1 expression in gastric cancer. In normal mucosa, stathmin1 was rarely detected. Interestingly, significant association of stathmin1 expression with more advanced stages, lymph node metastasis and vascular invasion was observed in the diffuse type of gastric cancer. Stathmin1 was also detected in invading gastric cancer cells. Moreover, the association of stathmin1 expression with the recurrence-free survival rate was more significant in the diffuse type of gastric cancer.

Furthermore, in this study, functional significance of stathmin1 was demonstrated in SNU638 and SNU16 cells. These results suggest that stathmin1 might be a good prognostic factor in the diffuse type of gastric cancer. Critical roles for stathmin1 in the proliferation of cancer cells, such as prostate cancer and osteosarcoma cells, have been demonstrated (Mistry and Atweh, 2006; Wang et al, 2007). In this study, we show, to the best of our knowledge, for the first time that stathmin1 regulates proliferation of poorly differentiated gastric cancer cells. Two mechanisms for stathmin1 regulation of microtubules and proliferation have been suggested (Rubin and Atweh, 2004).

Stathmin1 can bind two unpolymerised tubulin heterodimers and form a ternary stathmin�Ctubulin complex. This tubulin-sequestrating activity of stathmin prevents microtubule growth by diminishing the intracellular pool of tubulin Entinostat that is available for polymerisation. The other mechanism of stathmin regulation of proliferation is a catastrophe-promoting activity. Stathmin binds tubulin heterodimers at the microtubule ends and increases the rate of catastrophe through a GTP hydrolysis-dependent mechanism.