This could probably explain why more poorly differentiated gastric tumour tissues lack lamin A/C expression. Another important discovery in our study was that decreased expressions of lamin A/C was significantly correlated with poor patient outcome. Patients with gastric cancer who were lamin A/C protein-negative had a worse 5-year survival rate. Although there has been a great improvement in

the diagnosis and treatment with gastric cancer recently, it is still a major health problem and a leading cause of cancer mortality in Asian countries. To identify reliable prognostic markers in gastric cancer is therefore very important to guide surgical and chemotherapeutic S3I-201 supplier treatment according to individual risk. This finding suggested

that lamin A/C may have diagnostic and therapeutic potential for patients with gastric cancer in order to design optimal individual treatment modalities. The mechanism of tumour suppression by lamin A/C is not fully understood. Biochemical studies have shown that lamin A/C can interact with different gene regulators including SREBP1, MOK2 and the retinoblastoma protein (pRB) [26–28]. Excitingly, a series of experiments JQ1 concentration demonstrated that lamin A/C is necessary for a generally known tumour suppressor – pRB stabilization, and decreased expression of lamin A/C results in reduced activity of pRB [29–31]. pRB is a critical regulator of cell proliferation and differentiation and an important tumor suppressor.

In the G(1) phase of the cell cycle, pRB localizes to perinucleolar sites associated with lamin A/C intranuclear foci. Johnson et al[32] examined pRB function in cells lacking lamin A/C, finding that pRB levels are evidently decreased and that the remaining pRB is mislocalized. They demonstrated that A-type lamins protect pRB from proteasomal degradation. Both pRB levels and localization are restored upon reintroduction of lamin A. Lmna(-/-) cells resemble Rb(-/-) cells, ROS1 exhibiting altered cell-cycle properties and reduced capacity to undergo cell-cycle arrest in response to DNA damage. Their findings established a functional link between a core nuclear structural component and an important cell-cycle regulator. Recently, there was another report showing that protein levels of the oncoprotein gankyrin are elevated in Lmna-/- fibroblasts and Lmna-/- cells are refractory to p14arf-mediated cell cycle arrest, as was previously shown with p16ink4a [33]. These findings together with our data increase the possibility that lamin A/C might function as a tumour suppressor through function as a negative regulator of cell growth. However, the molecular mechanism underlying the loss of lamin A/C in human cancer remains unknown.