Jean-Claude Givel

Expression of homeobox-containing genes in primary and metastatic colorectal cancer

Homeobox genes are a network of genes encoding nuclear proteins functioning as transcriptional regulators. Human and murine homeobox genes of the HOX family are organised in four clusters on different chromosomes. Gene order within each cluster is highly conserved, perhaps in direct relation to their expression. Homeobox genes have recently been involved in normal development and oncogenesis. We have analysed HOX gene expression in normal human colon and in primary and metastatic colorectal carcinomas. The majority of HOX genes are active in normal adult colon and their overall expression pattern is characteristic of this organ. Furthermore, the expression of some HOX genes is identical in normal and neoplastic colon indicating that these genes may exert an organ-specific function. In contrast, other HOX genes exhibit altered expression in primary colon cancers and their hepatic metastases which may suggest an association with colon cancer progression.

Growth stimulation of a human colorectal carcinoma cell line by interleukin-1 and -6 and antagonistic effects of transforming growth factor β1

We analysed the effect of interleukin-1 (IL-1), IL-6 and transforming growth factor beta 1 (TGF beta 1) on the growth of a panel of eight colorectal carcinoma cell lines. IL-1 stimulated growth of two lines (LS411N and LS1034) up to 20-fold and IL-6 enhanced proliferation of LS1034 more than 5-fold. Both cytokines also augmented colony-formation of LS1034 in methylcellulose. Under both growth conditions IL-1 was the most potent stimulator. However, the addition of IL-6 to IL-1 synergistically enhanced proliferation of LS1034 in monolayer culture and additively augmented the number of colonies formed in methylcellulose. Furthermore, TGF beta 1 strongly reduced the growth rate of LS1034. Low amounts of TGF beta 1 markedly inhibited the response of LS1034 to IL-1 and totally abrogated proliferation induced by IL-6. We conclude that different cytokines can provide distinct signals for the regulation of growth of colorectal carcinoma cells.

Prognostic Value of Dukes and Jass Classifications of Colorectal Cancer

In an attempt to improve the prognostic accuracy for colon carcinoma, numerous alternative classifications have been proposed [1–13].