Overexpression of the rhoC gene correlates with progression of ductal adenocarcinoma of the pancreas

Abstract

Summary It has been reported that the rho genes, which consist of a ras-related small GTPase protein family, regulate cytoskeletal structures and have the potential to transform cultured cells. To investigate the biological relevance of the rho genes in pancreatic carcinogenesis, we examined expressions of the rhoA, B and C genes by polymerase chain reaction after reverse transcription (RT-PCR) in 33 cases of ductal adenocarcinoma of the pancreas. In addition, mutations of the K-ras, rhoA, B and C genes were studied in the same series of tumour tissues to correlate with rho gene expressions. The expression levels of the rhoC gene were significantly higher in tumours than in non-malignant portions (P < 0.001). Metastatic lesions overexpressed the rhoC gene compared with primary tumours (P < 0.05). Carcinoma tissues with perineural invasion and lymph node metastasis exhibited significantly higher expressions of the rhoC gene than tumours without these manifestations (P < 0.001 and P < 0.05 respectively). Overexpression of the rhoC gene significantly correlated with poorer prognosis of patients with pancreatic adenocarcinoma (P < 0.05). In contrast, the expression levels of the rhoA and B genes showed no significant relationship with clinicopathological findings. Mutation was not found either in the rhoA, B or C gene sequences examined. K-ras gene mutation, detected in 27 out of 33 (81.8%) cases, did not affect the expression levels in any of the rho genes. These suggest that elevated expression of the rhoC gene may be involved in the progression of pancreatic carcinoma independent of K-ras gene activation.

Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment

“…Rho-family GTPases function in cytoskeletal reorganization, cell migration, stress fiber formation and focal adhesion [137]. It is not surprising that enhanced expression of one of the Rho GTPase family members, RhoC, correlates with the progression of various tumor types to a metastatic phenotype [138,139]. In gene expression profiling experiments with melanoma variants of low or high metastatic potential, RhoC has been identified as a candidate involved in the spread of malignant cells.…”

Genomic analysis reveals RhoC as a potential marker in hepatocellular carcinoma with poor prognosis

“…The quality was checked in 1% agarose gels and the concentration was measured using an ultraviolet Spectrophotometer (Biochrom Ltd, Cambridge, England) (Suwa et al, 1998). The UV wavelength was adjusted at 260 nm.…”

“…Recently, emerging data suggest that RhoC gene may have a potential role in carcinogenesis and metastasis of tumour cells (Itoh et al, 1999;Clark et al, 2000). The expression level of RhoC in metastatic region of pancreatic cancer has been previously reported to be higher than primary lesion (Suwa et al, 1998). In addition, a genomic-wide analysis of gene expression revealed that RhoC gene was involved in vascular invasiveness of HCC (Okabe et al, 2001).…”

The activation of TC10, a Rho small GTPase, contributes to v-Rel-mediated transformation

“…Previous studies demonstrated that aberrant expression and activation of Rho small GTPases are important in tumor generation and progression, although mutation of Rho GTPase genes rarely occurs in tumors (Keely, 2001;Boettner and Van Aelst, 2002). Elevated expression of RhoA, RhoC, Rac1B and Rac2 were found in a variety of cancers including head and neck squamouscell cancers, ductal adenocarcinomas of the pancreas, inflammatory breast cancer cells, colon cancers and lung cancers (Suwa et al, 1998;van Golen et al, 2000;Abraham et al, 2001). Aberrant expression of Rho and Rac have been found in even moderately differentiated tumors, suggesting that Rho proteins may be early markers of tumor progression (Moscow et al, 1994;Suwa et al, 1998).…”

“…Elevated expression of RhoA, RhoC, Rac1B and Rac2 were found in a variety of cancers including head and neck squamouscell cancers, ductal adenocarcinomas of the pancreas, inflammatory breast cancer cells, colon cancers and lung cancers (Suwa et al, 1998;van Golen et al, 2000;Abraham et al, 2001). Aberrant expression of Rho and Rac have been found in even moderately differentiated tumors, suggesting that Rho proteins may be early markers of tumor progression (Moscow et al, 1994;Suwa et al, 1998). This report provides the first evidence that the overexpression of TC10 results in transformation of primary cells in culture.…”