Inverse relationship between TCTP/RhoA and p53/ /cyclin A/actin expression in ovarian cancer cells Inverse relationship between TCTP/RhoA and p53/ /cyclin A/actin expression in ovarian cancer cells

Abstract

The translationally controlled tumor protein (TCTP) plays a role in cell growth, cell cycle and cancer<br />progression. TCTP controls negatively the stability of the p53 tumor suppressor protein and interacts with the<br />cellular cytoskeleton. The deregulation of the actin and cytokeratin cytoskeleton is responsible for the increased<br />migratory activity of tumor cells and is linked with poor patient outcome. Recent studies indicate that cyclin A,<br />a key regulator of cell cycle, controls actin organization and negatively regulates cell motility via regulation of RhoA<br />expression. We studied the organization of actin and cytokeratin cytoskeleton and the expression of TCTP, p53,<br />cyclin A, RhoA and actin in HIO180 non-transformed ovarian epithelial cells, and OVCAR3 and SKOV3 (expressing<br />low level of inducible p53) ovarian epithelial cancer cells with different metastatic potential. Immunostaining<br />and ultrastructural analyses illustrated a dramatic difference in the organization of the cytokeratin and actin<br />filaments in non-transformed versus cancer cell lines. We also determined that there is an inverse relationship between<br />the level of TCTP/RhoA and actin/p53/cyclin A expression in ovarian cancer cell lines. This previously unidentified<br />negative relationship between TCTP/RhoA and actin/p53/cyclin A may suggest that this interaction is linked<br />with the high aggressiveness of ovarian cancers.The translationally controlled tumor protein (TCTP) plays a role in cell growth, cell cycle and cancer<br />progression. TCTP controls negatively the stability of the p53 tumor suppressor protein and interacts with the<br />cellular cytoskeleton. The deregulation of the actin and cytokeratin cytoskeleton is responsible for the increased<br />migratory activity of tumor cells and is linked with poor patient outcome. Recent studies indicate that cyclin A,<br />a key regulator of cell cycle, controls actin organization and negatively regulates cell motility via regulation of RhoA<br />expression. We studied the organization of actin and cytokeratin cytoskeleton and the expression of TCTP, p53,<br />cyclin A, RhoA and actin in HIO180 non-transformed ovarian epithelial cells, and OVCAR3 and SKOV3 (expressing<br />low level of inducible p53) ovarian epithelial cancer cells with different metastatic potential. Immunostaining<br />and ultrastructural analyses illustrated a dramatic difference in the organization of the cytokeratin and actin<br />filaments in non-transformed versus cancer cell lines. We also determined that there is an inverse relationship between<br />the level of TCTP/RhoA and actin/p53/cyclin A expression in ovarian cancer cell lines. This previously unidentified<br />negative relationship between TCTP/RhoA and actin/p53/cyclin A may suggest that this interaction is linked<br />with the high aggressiveness of ovarian cancers.