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Analysis of phosphorylation of pRB and its regulatory proteins in breast cancer.
  1. E Wakasugi,
  2. T Kobayashi,
  3. Y Tamaki,
  4. Y Nakano,
  5. Y Ito,
  6. I Miyashiro,
  7. Y Komoike,
  8. M Miyazaki,
  9. T Takeda,
  10. T Monden,
  11. M Monden
  1. Department of Surgery II, Osaka University Medical School, Japan.


    AIM: In order to study the role of retinoblastoma protein (pRB) in breast cancer, the phosphorylation of pRB and the expression of its related proteins-such as cyclin E, cyclin dependent kinase 2 (Cdk2), and p21/Cdk interacting protein 1 (Cip1)-were examined in 30 breast cancers in which pRB overexpression was confirmed immunohistochemically. METHODS: The phosphorylation of pRB for 30 tumours was investigated with western blotting. The expression of pRB, Cdk2/Cdc2, cyclin E, and p21/Cip1 was identified by immunohistochemistry and western blotting. RESULTS: The expression of pRB was confirmed in 52 of 70 tumours (74%) by immunostaining. Western blotting for pRB showed that 25 of 30 representative cancers (83%) were underphosphorylated, while only five tumours showed the hyperphosphorylated form of pRB. However, cyclin E and Cdk2-which promote phosphorylation of pRB-were expressed in all tumours. On the other hand p21/Cip1, a Cdk2 inhibitor, was expressed in 18 of 25 tumours with underphosphorylated pRB, while four of the five tumours with hyperphosphorylated pRB showed no expression of p21/Cip1. Examination of the relation between pRB phosphorylation and clinicopathological variables showed that the underphosphorylated group was characterised by low risk of lymph node metastasis (p < 0.01). CONCLUSIONS: The phosphorylation of pRB appears to be regulated mainly by p21/Cip1 through the suppression of cyclin E and Cdk2 in breast cancer. The underphosphorylated form of pRB may be useful as a prognostic factor.

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