title: Expression of pRB, cyclin/cyclin-dependent kinases and E2F1/DP-1 in human tumor lines in cell culture and in xenograft tissues and response to cell cycle agents.
abstract: OBJECTIVE
  Cell cycle regulatory components are interesting targets for cancer therapy. Expression of pRb, cyclin D1, cdk4, cyclin E, cdk2, E2F1 and DP-1 was determined in MCF-7 and MDA-MB-468 breast carcinoma cells, H460 and Calu-6 non-small cell lung carcinoma cells, H82 and SW2 small cell lung carcinoma cells, HCT116 and HT29 colon carcinoma cells and LNCaP and DU-145 prostate carcinoma cells.
  
  
  METHODS
  For Western blotting, the ratio with actin expression was used to normalize the data; all lines were run on the same gels.
  
  
  RESULTS
  In cell culture, pRb was not detected in MB-468 and H82 was low in SW2 and DU-145 and highest in HCT116; in tumors, pRb was not detected in MB-468, H82, SW2, and DU-145 and was highest in LNCaP and Calu-6. Cyclin D1 was not detected in SW2 cells in culture, was low in MB-468 and H82, and was highest in LNCaP and H460; in tumors, cyclin D1 was low in MB-468, H460, SW2 and DU 145, and was highest in LNCaP. In cell culture, cdk4 was lowest in Calu-6, HCT116, HT29 and DU-145 and highest in H82 and SW2; in tumors, cdk4 was low in MCF-7, MB-468, H460, Calu-6 and HCT116 and was very high in the SW2. Expression of cyclin E was very low in MCF-7 and HT29 and high in H460 in culture and was very low in MCF-7, H460, Calu-6, H82, HT29 and DU-145 in tumors and high in HCT116 and LNCaP. In cell culture, E2F1 was lowest in MB-468, Calu-6, HT29 and DU-145 cells and highest in LNCaP cells; in tumors, E2F1 was lowest in MCF-7, MB-468 and Calu-6 and highest in LNCaP. In cell culture, DP-1 was lowest in MB-468, HCT116 and HT29 and highest in SW2. The MCF-7 and MB-468 lines were most resistant to flavopiridol and olmoucine and the H460 and Calu-6 lines were most resistant to genistein. The SW2 tumor was most responsive to flavopiridol and olomoucine.
  
  
  CONCLUSIONS
  There is a high degree of variability in the expression of cell cycle components in human tumor cell lines, resulting in complexity in predicting response to cell cycle directed agents.
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
authors.forename: K
authors.initials: K
authors.lastname: Lu
authors.forename: C
authors.initials: C
authors.lastname: Shih
authors.forename: B A
authors.initials: BA
authors.lastname: Teicher
mesh_terms: D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins; D002470:Cell Survival / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016213:Cyclins / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007701:Kinetin; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D010880:Piperidines / Q000494:pharmacology; D010940:Plant Proteins / Q000096:biosynthesis*; D011687:Purines / Q000494:pharmacology; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002148:Calmodulin-Binding Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; C115911:EDF1 protein, human; C485470:Edf1 protein, mouse; D004791:Enzyme Inhibitors; D005419:Flavonoids; D010880:Piperidines; D010940:Plant Proteins; D011687:Purines; C107938:RRB1 protein, Zea mays; C493735:TFDP1 protein, human; C493736:Tfdp1 protein, mouse; D050680:Transcription Factor DP1; D014157:Transcription Factors; C077990:alvocidib; C090046:olomoucine; D019833:Genistein; D018844:Cyclin-Dependent Kinases; D007701:Kinetin