Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human Polycomb-group (PcG) genes play a crucial role in the regulation of embryonic development and regulation of the cell cycle and hematopoiesis. PcG genes encode proteins that form two distinct PcG complexes, involved in maintenance of cell identity and gene silencing patterns. We recently showed that expression of the BMI-1 and EZH2 PcG genes is separated during normal B-cell development in germinal centers, whereas Hodgkin/Reed-Sternberg (H/RS) cells co-express BMI-1 and EZH2. In the current study, we used immunohistochemistry and immunofluorescence to determine whether the binding partners of these PcG proteins are also present in H/RS cells and H/RS-derived cell lines. PcG expression profiles were analyzed in combination with expression of the cell cycle inhibitor p16INK4a, because experimental model systems indicate that p16 is a downstream target of Bmi-1. We found that H/RS cells and HL-derived cell lines co-express all core proteins of the two known PcG complexes, including BMI-1, MEL-18, RING1, HPH1, HPC1, and -2, EED, EZH2, YY1, and the HPC2 binding partner, CtBP. Expression of HPC1 has not been found in normal mature B cells and other malignant lymphomas of B-cell origin, suggesting that the PcG expression profile of H/RS is unique. In contrast to Bmi-1 transgenic mice where p16INK4a is down-regulated, 27 of 52 BMI-1POS cases of HL revealed strong nuclear expression of p16INK4a. We propose that abnormal expression of BMI-1 and its binding partners in H/RS cells contributes to development of HL. However, abnormal expression of BMI-1 in HL is not necessarily associated with down-regulation of p16INK4a.
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PMID:Unique polycomb gene expression pattern in Hodgkin's lymphoma and Hodgkin's lymphoma-derived cell lines. 1498 41

In spite of the known function of polycomb group (PcG) genes in stem cell self-renewal, control of cellular proliferation and differentiation, its role in cancer pathogenesis is still poorly understood. We studied the expression by immunohistochemistry of several PcG-maintenance complex proteins (RING1, RNF2, BMI1, MEL18, HPH1 and RYBP) in nontumoral (154 samples) and tumoral (550 samples) human tissues using Tissue Microarrays. For selected genes (BMI1 and RING1) FISH analysis has been also carried out. PcG proteins had a tissue- and cell-type-specific expression pattern. Some of them were highly selectively expressed, such as HPH1, which was detected in germ cells in testis, pituitary and parathyroid glands and Langerhans islets, and RYBP, which was found in placenta, umbilical cord and thyroid gland. By contrast, RING1 was ubiquitously expressed in every normal tissue analyzed. Changes in expression associated with tumoral transformation have been found for BMI1 and RNF2, which exhibited increased expression in a large series of tumors, including gastrointestinal tumors, pituitary and parathyroid adenomas, and lymphomas, compared with their expression in normal-cell counterparts. The high level of expression of BMI1 protein observed in mantle-cell lymphomas and pituitary adenomas is associated in some cases with amplification of BMI1 locus. These findings imply that upregulation of BMI1 may constitute a malignancy marker in different types of cancer, mainly in lymphoid and endocrine tumors. RING1 was lost in a group of renal-cell carcinomas and testicular germ-cell tumors. Lastly, RYBP is anomalously expressed in Hodgkin's lymphomas and oligodendrogliomas, among others tumors. A significant finding of the study is the identification of unique PcG profiles for some tumors, such as testicular germ-cell tumors, which have high levels of HPH1 expression and loss of RING1 and/or BMI1; pituitary adenomas, which expressed every PcG protein analyzed; and clear-cell renal-cell carcinoma, which was the only tumor other than testicular germ-cell tumors that did not express RING1.
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PMID:Variability in the expression of polycomb proteins in different normal and tumoral tissues. A pilot study using tissue microarrays. 1652 73