Protein Phosphatase 2A (PP2A), a widely conserved protein serine/threonine Phosphatase (PSP), has recently been experimentally established as one of the important tumour suppressors in humans. It has been experimentally shown to be a prerequisite for human cell transformation (Westermarck and Hahn, 2008; Janssens et al., 2005). Moreover, dephosphorylation by PP2A of the target molecules which are critical for its tumour suppressor activity, have been recently identified.
Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A), a PP2A inhibiting oncoprotein recently identified by our research group, promotes malignant cell growth and cellular transformation. Additionally, CIP2A was shown to be over expressed in human head and neck squamous cell carcinomas (HNSCC) and in colon cancer as compared to control tissue (Junttila et al.,2007). However, the mechanisms of regulation and its role in human malignancies are not clear. We have attempted to address these questions by investigating expression and role of CIP2A in gastric carcinogenesis. Over expression of c-Myc has been shown previously to play a contributing role in gastric carcinogenesis. But a majority of the studies are limited to the role of c-Myc amplifications, which in turn holds true for less than 20 % of gastric cancers with c-Myc protein over expression. Therefore, other mechanisms by which c-Myc may play a role are still unknown.
We demonstrate, for the first time, the prognostic role of CIP2A in gastric cancer patients along with its role in promoting cell proliferation and c-Myc stability in gastric cancer cells. Interestingly, we identify c-Myc as one of the first stimulator of CIP2A expression in these cells, thereby establishing a positive feedback mechanism between the two human oncoproteins. Additionally, there is co-expression of both the human oncoproteins in human gastric cancer specimens.
Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A), a PP2A inhibiting oncoprotein recently identified by our research group, promotes malignant cell growth and cellular transformation. Additionally, CIP2A was shown to be over expressed in human head and neck squamous cell carcinomas (HNSCC) and in colon cancer as compared to control tissue (Junttila et al.,2007). However, the mechanisms of regulation and its role in human malignancies are not clear. We have attempted to address these questions by investigating expression and role of CIP2A in gastric carcinogenesis. Over expression of c-Myc has been shown previously to play a contributing role in gastric carcinogenesis. But a majority of the studies are limited to the role of c-Myc amplifications, which in turn holds true for less than 20 % of gastric cancers with c-Myc protein over expression. Therefore, other mechanisms by which c-Myc may play a role are still unknown.
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