Significance of Apoptosis in the Process of Tumorigenesis in Colorectal Mucosa and Adenomas in FAP Patients

The relation between proliferation and apoptosis was studied in colorectal mucosal biopsies (N=41), tubular adenomas (TA) (N=104) and tubulovillous adenomas (TVA) (N=34) from 37 FAP patients. Proliferative activity was determined by cell cycle distribution analysis. In addition, transcriptional capacity was determined by chromatin in situ testing. For both, DNA flow cytometry was used. Cycling cells were identified by immunohistochemical staining with monoclonal antibody Ki67. The existence of subdiploid apoptotic cells was derived from DNA and/or DNA/protein patterns. In a follow‐up group, the mucosa is characterised by a balance between proliferation (S % + G2M % = 19) and apoptotic cells (% = 17). The percentage of Ki67 positive cells (16%) corresponds to the percentages mentioned above. In TA, the amount of apoptotic cells remains unaltered, in TVA it decreases to 8%. At the same time, the percentage of Ki67 positive cells increases significantly in both TA and TVA (39%, 42%). With patients who underwent surgery due to clinical signs without histological evidence for malignancy, apoptotic cells in TA continue to decrease significantly (9%), without any changes in cycling cells. Only in the carcinoma‐bearing bowel, cycling cells increase to 52%. Here, the percentage of apoptotic cells in TVA reaches the lowest level (5%). A connection between proliferation and apoptosis was observed in mucosa and TVA. The process of tumorigenesis is characterised by a stepwise increase in resistance to apoptosis followed by an increase in cycling cells

Tumor Suppressor Activity of Profilin Requires a Functional Actin Binding Site

Profilin 1 (PFN1) is a regulator of the microfilament system and is involved in various signaling pathways. It interacts with many cytoplasmic and nuclear ligands. The importance of PFN1 for human tissue differentiation has been demonstrated by the findings that human cancer cells, expressing conspicuously low PFN1 levels, adopt a nontumorigenic phenotype upon raising their PFN1 level. In the present study, we characterize the ligand binding site crucial for profilin's tumor suppressor activity. Starting with CAL51, a human breast cancer cell line highly tumorigenic in nude mice, we established stable clones that express PFN1 mutants differentially defective in ligand binding. Clones expressing PFN1 mutants with reduced binding to either poly-proline-stretch ligands or phosphatidyl-inositol-4,5-bisphosphate, but with a functional actin binding site, were normal in growth, adhesion, and anchorage dependence, with only a weak tendency to elicit tumors in nude mice, similar to controls expressing wild-type PFN1. In contrast, clones expressing a mutant with severely reduced capacity to bind actin still behaved like the parental CAL51 and were highly tumorigenic. We conclude that the actin binding site on profilin is instrumental for normal differentiation of human epithelia and the tumor suppressor function of PFN1

Rome et l’Occident

Cet ouvrage collectif étudie les relations multiformes qui se sont établies entre Rome et l’Occident depuis la création des provinces d’Hispanie en 197 av. J.-C. jusqu’à la mort de l’empereur Commode en 192 ap. J.-C. L’espace pris en considération comprend les îles de la Méditerranée occidentale (Sicile, Sardaigne, Corse), la péninsule Ibérique, la Gaule (Cisalpine exclue), la Germanie, les Alpes (provinces alpestres, Rhétie) et la Bretagne romaine. Au cœur des questionnements se trouve le mode de fonctionnement de l’Empire romain. La longue durée retenue – près de quatre siècles – permet de mieux saisir les évolutions qui se manifestèrent dans les régions occidentales en relation avec la conquête romaine et à sa suite, mais aussi les continuités que le passage de la République à l’Empire ne fit pas disparaître. Frédéric Hurlet a réuni une équipe internationale de chercheurs français, allemands et anglo-saxons. Dix-huit contributions ont été rassemblées pour analyser les différents aspects de l’emprise de Rome sur l’Occident dans une perspective qui mêle les approches thématiques et géographiques. Le manuel est divisé en deux parties. La première étudie les structures qui permirent à l’Empire romain de dominer un aussi vaste espace. On y trouve des synthèses sur la loi provinciale, les gouverneurs, l’armée, la circulation des hommes et de l’information, la fiscalité, le cens, l’exercice de la justice et la monnaie. La seconde partie adopte une perspective géographique en étudiant différentes régions de l’Occident dans leurs relations avec Rome. Quatre thématiques principales y sont développées : des synthèses régionales (Lusitanie, Trois Gaules), le statut des cités et des personnes (Gaules), la cité comme cellule de base de l’Empire (Bretagne, Germanie, Rhétie) et la religion (Germanie, Bretagne)