Analysis of phosphorylation of pRB and its regulatory proteins in breast cancer.

Abstract

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 p2l/Cdk interacting protein 1 (Cipl)-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 p2lICipl 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/Cipl, 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 p2l/Cipl. 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 p2lICipl through the suppression of cyclin E and Cdk2 in breast cancer. The underphosphorylated form ofpRB may be useful as a prognostic factor. (3 Clin Pathol 1997;50:407-412)

The prognostic value of the AgNOR parameter in human breast cancer depends on the pRb and p53 status

“…These findings are consistent with those previously reported for AgNORs, 9 , p53, 27 28 and pRb. [29][30][31] In the whole series of breast cancers the three parameters were significantly associated with DFS. However, in node negative cancers, only the pRb variable had significant prognostic value.…”

RB family members as predictive and prognostic factors in human cancer

“…This can be explained by the fact that pRb loss enhances cell division rather than cell motility, which in breast cancer is mostly mediated by other factors such as ErbB-2 expression. Only two studies have identified a direct relationship between pRb status and nodal involvement (Sawan et al, 1992;Spandidos et al, 1992); whereas, Wakasugi et al (1997) showed that the underphosphorylated (active) form of pRb was related to low risk of lymph node metastasis (Po0.01).…”

Cyclin D1 and human neoplasia

“…In this situation, assessment of cyclin D1 protein in combination with pRB may provide more useful information. [84][85][86] The publication about cyclin D1 in DCIS followed a previous paper 87 by the same group in which overexpression of cyclin D mRNA, determined by in situ hybridisation, was able to distinguish DCIS from atypical ductal hyperplasia and other lesions associated with a low risk of progression to invasive carcinoma.…”