Tiam1 activates the Rho‐like GTPase Rac1, and studies indicate that Tiam1–Rac1 signaling affects invasion in different ways depending on the cell type studied. However, no investigations on Tiam1 in human tumors have been reported. Here, we show that for 4 of 5 human renal‐cell carcinoma (RCC) cell lines the expression levels of Tiam1 tended to be inversely correlated with in vitro invasiveness, whereas no obvious correlation could be found between the expression levels of Rac1 and invasion. Subsequent mutation analysis of these cell lines revealed no mutations in Rac1 but up to 5 different point mutations in the Tiam1 gene. Of these, 1 mutation (A441G) was located in the NH2‐terminal pleckstrin homology domain, which is essential for membrane localization and functional activity of Tiam1. By analysis of an additional 30 primary human RCCs, mutation A441G was found in 4 of 35 tumors and tumor cell lines (11.5%) but not in the respective normal kidney tissues. By enzymatic digestion, mutation A441G proved to be heterozygous, suggesting a dominant active function. This was supported by showing that stable over‐expression of mutated A441G‐Tiam1 induced transformation of NIH3T3 cells, as determined in a colony formation assay, whereas empty vector and wild‐type Tiam1 failed to do so. In conclusion, a distinct Tiam1 mutation (A441G) was identified in several human RCCs. This mutation induced transformation of NIH3T3 cells and, hence, might play a major role in the progression of human RCCs. Further analyses on Tiam1 mutations in human tumors might give new clues to their role in tumor progression. Int. J. Cancer 88:369–376, 2000. © 2000 Wiley‐Liss, Inc.

Paramyosin, although a widely distributed muscle component among invertebrates, has hitherto not clearly been shown to occur in the muscles of schistosomes. Instead, it has been reported to occur in the tegument. In the present study, a specific antibody reacting with each of 10 isoforms of paramyosin was used for light microscopical immunolocalization in sections of Schistosoma mansoni. Specimens were fixed by a new method to immobilize antigens with uranyl acetate-trehalose-methanol. In cercariae, schistosomula, and adults, the circular and longitudinal muscles of the body wall, the dorsoventral muscles and those surrounding the gut and the pharynx as well as the fast moving cross-striated muscles of the tail of cercariae intensely reacted with the antibody. However, neither immunohistologically nor on Western blots of isolated tegument, were indications found for the presence of paramyosin in the tegument. In vivo phosphorylation and binding of anti-phospho-tyrosine and anti-phospho-serine antibodies show phosphorylation of paramyosin which probably is responsible for the generation of the isoforms.

A novel gene fragment (ELISC-1) and three known genes were identified as potential regulators of tumour invasiveness. Cloning of the entire sequence of ELISC-1 and subsequent investigations are required to establish its biological role.