Alignment studies performed with characterized MMTV and human breast cancer betaretrovirus amino acid sequences revealed a 93% to 99% identity with the p27 capsid proteins, a 93% to 97% identity with the betaretrovirus envelope proteins, and a 76% to 85% identity with the more variable superantigen proteins.
In order to elucidate the possible role of p27 mutations in the development or progression of human breast cancer, we have studied the occurrence of genetic abnormalities in this gene in a series of 30 primary breast carcinomas.
These data indicate that p27 mutations are a rare event in breast cancer, but may play an important role in the development of a minority of these cancers.
In conclusion, the polymorphic variant at codon 109 of p27 gene may not be a marker for determining patients' risk of developing breast cancer but it may be a potential genetic marker for poor prognosis, thereby a marker for tumor prognosis.
Collectively, these results demonstrate an unprecedented connection between p27, Pitx2 and p21 relevant for the regulation of cell cycle progression and cancer and for understanding human pathologies associated with p27 germline mutations.
Additionally, 60 DTCs-related microarray and RNA-seq datasets were obtained to investigate the expression level and clinical value of p27 gene in DTCs patients.
When the role of SCF<sup>Skp2/Cks1</sup>-mediated p27 ubiquitination in cancer was specifically tested by p27Thr187-to-Ala knockin (p27T187A KI), it was found dispensable for Kras<sup>G12D</sup>-induced lung tumorigenesis but essential for Rb1-deficient pituitary tumorigenesis.
Cell cycle deregulation is common in human cancer, and alterations of p27 and p21, two critical cell cycle regulators, have been implicated in the development of many human malignancies.
Defect of spindle checkpoint gene Mad2 and mutation of p27 gene are involved mainly in colorectal carcinogenesis and associated with prognosis of colorectal cancer.
Nuclear FGFR2 expression was associated with increased risk of metastasis (odds ratio (OR)=7.61, P=0.008), as was membranous PDGFRα (OR=13.71, P=0.015), membranous VEGFR1 (OR=8.01, P=0.037), nuclear MIB1 (OR=1.26, P=0.008), and cytoplasmic p27 (OR=1.037, P=0.030).
Expression of the p27 protein did not correlate with CDKN1B mutation status, and no differences in the clinical characteristics between CDKN1B mutated and CDKN1B wild type tumor carriers were found.
The activity of the endogenous kinase carrying the E17K mutation immunoprecipitated by tumour tissue was significantly higher compared with the wild-type kinase immunoprecipitated by the adjacent normal tissue as determined both by in vitro kinase assay using a consensus peptide as substrate and by in vivo analysis of the phosphorylation status of AKT1 itself (pT308, pS473) or of known downstream substrates such as GSK3 (pS9/S22) and p27 (T198).
Our findings suggest that the p27 109GG variant genotype may not play a major role in the etiology of SCCHN but may be associated with an increased risk in at-risk subgroups or subsets of SCCHN, particularly oral cavity cancer and possibly tumor progression.
When individuals with variant-containing genotypes were compared with homozygous wild-type carriers, a significantly increased lung cancer risk was identified for polymorphisms in p53 intron 6 [rs1625895; odds ratio (OR), 1.29; 95% confidence interval (95% CI), 1.08-1.55] and in p27 5' untranslated region (UTR; rs34330; OR, 1.27; 95% CI, 1.01-1.60).