Increased expression of the EZH2 polycomb group gene in BMI-1-positive neoplastic cells during bronchial carcinogenesis.

Polycomb group (PcG) genes are responsible for maintenance of cellular identity and contribute to regulation of the cell cycle. Recent studies have identified several PcG genes as oncogenes, and a role for PcG proteins in human oncogenesis is suspected. We investigated the expression of BMI-1 and EZH2 PcG oncogenes in human bronchial squamous cell carcinomas (SCCs) and bronchial premalignant precursor lesions (PLs). Whereas normal bronchial epithelium was associated with widespread expression of BMI-1 in resting EZH2-negative cells, neoplastic cells in lung carcinomas displayed altered expression of both BMI-1 and EZH2. Two patterns of abnormal PcG expression were observed: increased expression of BMI-1 in dividing neoplastic cells of PLs and SCCs, and enhanced expression of EZH2 and Ki-67 in BMI-1-positive cells according to severity of the histopathologic stage. We propose that altered expression of BMI1 and EZH2 is an early event that precedes high rates of proliferation in lung cancer. Because PcG complexes are normally involved in the maintenance of cell characteristics, abnormal PcG expression may contribute to loss of cell identity

Usage of TCRAV and TCRBV gene families in human fetal and adult TCR rearrangements

We have investigated fetal and adult T-cell receptor (TCR) A and B V-gene repertoires both by fluorescence-activated cell sorter (FACS) analysis with the avialable TCR V region-specific mAbs and by the polymerase chain reaction (PRC) with TRC V gene family-specific oligonucleotides. Among the low number of CD3+ T cells, most of the TRC V region tested for could be detected by FACS analysis in liver, bone marrow, and spleen derived from a 14-week-old fetus and two 15-weeks-old fetuses. Similarly, the PCR analysis showed that the majority of the TCRAV and TCRBV families were expressed in the peripheral organs of the 13-week-old fetus, although an apparent absence of particular TCR V families was found in liver and bone marrow. This was most probably the consequence of the low number of CD3+ T cells in these organs. In 17-week-old week-old fetal thymi the level of expression of some TCRAV and TCRBV gene families, in particular those that contain single member, was lower compared to post-partum thymi and adult peripheral blood mononuclear cells. The combined data of FACS and PCR analysis demonstrate that TCR genes belonging to the majority of TCR V gene families can be used in TCR α and β chain rearrngements during early human fetal life. Our data also suggest that the expression levels of some of the single member TCR V gene families may be influenced by the development stage

Self-renewal of hematopoietic and leukemic stem cells: a central role for the Polycomb-group gene Bmi-1.

Self-renewal of hematopoietic stem cells is vital for the sustained daily production of blood cells. Two recent studies have shown that the Polycomb-group gene Bmi-1 is indispensable for regulation of self-renewal by normal and leukemic stem cells. This identifies Polycomb-group genes as potential targets for therapeutic intervention in leukemia, and possibly other forms of cancer