PMID- 15660415
OWN - NLM
STAT- MEDLINE
DCOM- 20050714
LR  - 20091119
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 93
IP  - 4
DP  - 2004 Nov 1
TI  - Abnormal cell cycle regulation in primary human uveal melanoma cultures.
PG  - 708-20
AB  - Uveal malignant melanoma is the most frequent primary intraocular tumor in adult 
      humans. The cellular events leading to neoplasic transformation of normal uveal 
      melanocytes are not well known when compared to other cancers. In this study, we 
      investigated the role of G1 and G1/S regulatory proteins of the cell cycle in 
      human uveal melanoma (UM) primary cell cultures, since these proteins are common 
      targets in tumor development. Further, freshly established and characterized 
      tumor cells are a better model for in vitro studies when compared to cell lines 
      established long ago. Human primary cell cultures from eight different UM were 
      established, as well as one primary culture from rhesus uveal normal melanocytes 
      (UNM). Primary human UM cultures were characterized by a low establishment and 
      growing rate. From four successful cultures, three showed a high expression of 
      cyclin D1, cyclin E, p16NK4A, and p27KIP1 with no variations in cyclin A, 
      cyclin-dependent kinase 2 (CDK2), and CDK4. Interestingly, in one of the cultured 
      tumors, tumor suppressor protein retinoblastoma (Rb) did not bind E2F despite the 
      fact that Rb was found in its hypophosphorylated form. No mutations in either RB1 
      or the Rb-binding pocket of E2F-1 were detected. Furthermore, we identified seven 
      proteins co-immunoprecipitating with Rb in this tumor, including Lamin A/C and 
      six proteins not previously reported to bind Rb: Hsc70, high mobility group 
      protein 1 (HMG-1), hnRPN, glyceraldehyde 3 phosphate dehydrogenase (G3PDH), EF-1, 
      and EF-2. Our results indicate that the overexpression of cyclins D1/E and CDKIs 
      p16 and p27, together with a deregulation of the Rb/E2F pathway, may be 
      implicated in the development of human UM.
FAU - Pardo, Maria
AU  - Pardo M
AD  - Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, 
      South Parks Road, Oxford, OX1 3QU, UK. maria.pardo-perez@bioch.ox.ac.uk
FAU - Pineiro, Antonio
AU  - Pineiro A
FAU - de la Fuente, Maria
AU  - de la Fuente M
FAU - Garcia, Angel
AU  - Garcia A
FAU - Prabhakar, Sripadi
AU  - Prabhakar S
FAU - Zitzmann, Nicole
AU  - Zitzmann N
FAU - Dwek, Raymond A
AU  - Dwek RA
FAU - Sanchez-Salorio, Manuel
AU  - Sanchez-Salorio M
FAU - Dominguez, Fernando
AU  - Dominguez F
FAU - Capeans, Carmen
AU  - Capeans C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Carrier Proteins)
RN  - 0 (Cyclins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Retinoblastoma Protein)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Carrier Proteins/physiology
MH  - Cell Cycle/*physiology
MH  - Choroid Neoplasms/*physiopathology
MH  - Cyclin-Dependent Kinases/physiology
MH  - Cyclins/*physiology
MH  - DNA-Binding Proteins/physiology
MH  - Humans
MH  - Macaca mulatta
MH  - Melanocytes/cytology
MH  - Melanoma/*physiopathology
MH  - Middle Aged
MH  - Retinoblastoma Protein/physiology
MH  - Tumor Cells, Cultured
EDAT- 2005/01/22 09:00
MHDA- 2005/07/15 09:00
CRDT- 2005/01/22 09:00
PHST- 2005/01/22 09:00 [pubmed]
PHST- 2005/07/15 09:00 [medline]
PHST- 2005/01/22 09:00 [entrez]
AID - 10.1002/jcb.20230 [doi]
PST - ppublish
SO  - J Cell Biochem. 2004 Nov 1;93(4):708-20. doi: 10.1002/jcb.20230.