Centrosome-centriole abnormalities are markers for abnormal cell divisionsand cancer in the transgenic adenocarcinoma mouse prostate (TRAMP) model

We utilized the transgenic adenocarcinoma mouse prostate (TRAMP) model to s tudy the formation of abnormal mitosis in malignant tumors of the prostate. The results presented here are focused on centrosome and centriole abnorma lities and the implications for abnormal cell divisions, genomic instabilit y, and apoptosis. Centrosomes are microtubule organizing organelles which a ssemble bipolar spindles in normal cells but can organize mono-, tri-, and multipolar mitoses in tumor cells, as shown here with histology and electro n microscopy in TRAMP neoplastic tissue. These abnormalities will cause une qual distribution of chromosomes and can initiate imbalanced cell cycles in which checkpoints for cell cycle control are lost. Neoplastic tissue of th e TRAMP model is also characterized by numerous apoptotic cells. This may b e the result of multipolar mitoses related to aberrant centrosome formation s. Our results also reveal that centrosomes at the poles in mitotic cancer cells contain more than the regular perpendicular pair of centrioles which indicates abnormal distribution of centrioles during separation to the mito tic poles. Abnormalities in the centriole-centrosome complex are also seen during interphase where the complex is either closely associated with the n ucleus or loosely dispersed in the cytoplasm. An increase in centriole numb ers is observed during interphase, which may be the result of increased cen triole duplication. Alternatively, these centrioles may be derived from bas al bodies that have accumulated. in the cell's cytoplasm, after the loss of cell borders. The supernumerary centrioles may participate in the formatio n of abnormal mitoses during cell division. These results demonstrate multi ple abnormalities in the centrosome-centriole complex during prostate cance r that result in abnormal mitoses and may lead to increases in genomic inst ability and/or apoptosis. (C) 2000 Editions scientifiques et medicales Else vier SAS.