Variability in the expression of polycomb proteins in different normal and tumoral tissues. A pilot study using tissue microarrays.
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.
Sánchez-Beato
Margarita
M
Lymphoma Group, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain. msbeato@cnio.es
Sánchez
Esther
E
González-Carreró
Joaquín
J
Morente
Manuel
M
Díez
Ana
A
Sánchez-Verde
Lydia
L
Martín
María Carmen
MC
Cigudosa
Juan C
JC
Vidal
Miguel
M
Piris
Miguel A
MA
D002352:Carrier Proteins / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D010865:Pilot Projects; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D012097:Repressor Proteins / Q000032:analysis* / Q000235:genetics; D046888:Tissue Array Analysis / Q000379:methods*; D044767:Ubiquitin-Protein Ligases
C069077:BMI1 protein, human; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C489348:PCGF2 protein, human; C491239:PHC1 protein, human; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins; C434957:RYBP protein, human; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1; C080355:RING1 protein, human; C489841:RNF2 protein, human; D044767:Ubiquitin-Protein Ligases