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

Cancer Chemother Pharmacol. 2000;46(4):293-304. doi: 10.1007/s002800000136.

Abstract

Purpose: 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.

MeSH terms

  • Aged
  • Animals
  • Antineoplastic Agents / pharmacology
  • Blotting, Western
  • Calmodulin-Binding Proteins / biosynthesis*
  • Cell Cycle / drug effects
  • Cell Cycle Proteins*
  • Cell Survival / drug effects
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / biosynthesis*
  • Cyclins / biosynthesis*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Flavonoids / pharmacology
  • Genistein / pharmacology
  • Humans
  • Kinetin
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Transplantation
  • Piperidines / pharmacology
  • Plant Proteins / biosynthesis*
  • Purines / pharmacology
  • Transcription Factor DP1
  • Transcription Factors / biosynthesis*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Calmodulin-Binding Proteins
  • Cell Cycle Proteins
  • Cyclins
  • EDF1 protein, human
  • Edf1 protein, mouse
  • Enzyme Inhibitors
  • Flavonoids
  • Piperidines
  • Plant Proteins
  • Purines
  • RRB1 protein, Zea mays
  • TFDP1 protein, human
  • Tfdp1 protein, mouse
  • Transcription Factor DP1
  • Transcription Factors
  • alvocidib
  • olomoucine
  • Genistein
  • Cyclin-Dependent Kinases
  • Kinetin