Identification of MMTV-associated p14 proteins in benign breast tissues confirms prior PCR-based studies that MMTV infection occurs before the development of MMTV positive breast cancer.
Expression of ANRIL-Polycomb Complexes-CDKN2A/B/ARF Genes in Breast Tumors: Identification of a Two-Gene (EZH2/CBX7) Signature with Independent Prognostic Value.
We conclude that YB-1 cooperates with p300 to allow BMI1 to over-ride p16(INK4a) -mediated cell cycle arrest enabling self-renewal and the development of aggressive breast tumors.
Expression of ANRIL mainly coclustered with p14/ARF both in physiologic (various normal human tissues) and in pathologic conditions (human breast tumors).
These results demonstrate a causal role of p16(INK4A) disruption in modulating DNA hypermethylation, and identify a dynamic and active process whereby epigenetic modulation of gene expression is activated as an early event in breast tumor progression.
Finally, the results indicate that these proteins are often co-altered in primary breast tumours and that p16INK4a and p14ARF had non-independent behaviour, since they were silenced or overexpressed concomitantly with a significant correlation (p < 0.05).
These data suggest that DNA methylation of the p16 gene in some breast tumours could be the result of an active process that generates a discrete methylation pattern and, hence, could ultimately be amenable to therapeutic manipulation.
Our results suggest that the MTS1 gene is not mutated with increased frequency in primary breast tumors, and thus may not play a major role in breast carcinogenesis.