Increased expression of the P27KIP1 protein in human esophageal cancer cell lines that over-express cyclin D1

Carcinogenesis. 1997 Jun;18(6):1139-48. doi: 10.1093/carcin/18.6.1139.


In the present study we have characterized eight human esophageal squamous carcinoma cell lines for levels of expression of cyclins D1, E, A and B1; CDKs 1, 2 and 4; the CDK inhibitors p16INK4, p21WAF1 and p27KIP1; the retinoblastoma (Rb) protein; and in vitro CDK2- and CDK4-associated kinase activity; and also compared the growth properties of these cell lines. The level of the cyclin D1 protein varied by over 30-fold amongst the eight cell lines. The high level in two cell lines was associated with amplification of this gene, but in three cell lines it was due to post-transcriptional events. Amongst the eight cell lines there was a significant correlation between the levels of cyclin D1, Rb and p27KIP1 proteins, and CDK4-associated kinase activity. Furthermore, when an exogenous cyclin D1 cDNA was over-expressed in the EC109 cell line by transfection, this led to increased expression of both Rb and p27KIP1. There was, however, no correlation between the level of cyclin D1 expression and the cell doubling times, duration of the G1 phase, or colony-forming efficiency in agar. Two of the cell lines displayed a high level of the cyclin E protein, low levels of cyclin D1, lacked expression of the Rb protein and expressed high levels of the p16INK4 protein. One of these cell lines displayed amplification of the latter gene. There was no correlation between the levels of cyclins E or A and in vitro CDK2 kinase activity, but CDK2 kinase activity was inversely correlated with the duration of the G1 phase of the cell cycle. Taken together, these studies indicate marked heterogeneity in the expression of cell cycle-related proteins amongst a series of esophageal carcinoma cell lines. The correlation between the levels of the cyclin D1, Rb and p27Kip1 proteins suggest the existence of a homeostatic feedback loop between positive and negative acting components of the cell cycle machinery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Northern
  • Blotting, Southern
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / metabolism
  • Cell Cycle / physiology
  • Cell Cycle Proteins*
  • Cell Division / physiology
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / biosynthesis
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / biosynthesis*
  • Cyclins / metabolism
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Humans
  • Microtubule-Associated Proteins / biosynthesis*
  • Oncogene Proteins / biosynthesis*
  • Oncogene Proteins / metabolism
  • Retinoblastoma Protein / biosynthesis
  • Retinoblastoma Protein / metabolism
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*


  • Carrier Proteins
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclins
  • Microtubule-Associated Proteins
  • Oncogene Proteins
  • Retinoblastoma Protein
  • Tumor Suppressor Proteins
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases