P53 and rb alterations in primary breast-carcinoma - correlation with hormone receptor expression and lymph-node metastases

Expression of Rb and mutant p53 nuclear phosphoproteins was analyzed immunohistochemically in 69 breast cancer patients. Results were correlated with hormone receptor ( ER and PR ) and lymph node ( LN ) status. There was a significant association between the immunohistochemical evidence of p53 and/or Rb alterations and loss of hormone receptor expression. Mutations in p53 and/or low level Rb expression were not associated with the presence of axillary lymph node metastases. However, in patients with hormone receptor positive tumors, there was statistically significant correlation between altered expression of p53 and/or Rb and the presence of LN metastases. These results indicate that: (i) loss of steroid hormone receptor expression (and thus loss of hormonal growth control) is accompanied by somatic inactivation of the p53 or Rb tumor suppressor genes; and (ii) in tumors that remain under hormonal growth regulation inactivation of p53 and/or Rb may play a role in tumor progression

Dyskeratosis congenita and cancer in mice deficient in ribosomal RNA modification.

Mutations in DKC1 cause dyskeratosis congenita (DC), a disease characterized by premature aging and increased tumor susceptibility. The DKC1 protein binds to the box H + ACA small nucleolar RNAs and the RNA component of telomerase. Here we show that hypomorphic Dkc1 mutant (Dkc1m) mice recapitulate in the first and second generations (G1 and G2) the clinical features of DC. Dkc1m cells from G1 and G2 mice were impaired in ribosomal RNA pseudouridylation before the onset of disease. Reductions of telomere length in Dkc1m mice became evident only in later generations. These results suggest that deregulated ribosome function is important in the initiation of DC, whereas telomere shortening may modify and/or exacerbate DC