In the present study we analyzed the effect of simultaneous FOXO3 silencing and p27Kip1 activation on breast cancer cell survival and the potential targets of these changes in cancer molecular pathways.
High p27Kip1 expression was an independent predictor of responsiveness to hormonal therapy and thus may be useful for the selection of premenopausal women with early-stage hormone receptor-positive breast cancer for adjuvant combination endocrine therapy.
The 95% confidence intervals for per allele risk estimates excluded a twofold risk, indicating that common CDKN1B polymorphisms do not markedly modifybreast cancer risk among BRCA1 or BRCA2 carriers.
In a parsimonious multivariable proportional hazards model, protein levels of cyclin E, p27(Kip1), p53, and the presence of glomeruloid microvascular proliferation all independently predicted outcome after breast cancer.
Elevated levels of the cell cycle protein cyclin E, and low levels of its inhibitor, p27(Kip1), have been associated with a poor prognosis following breast cancer.
While in vitro, following release of breast cancer cell lines from serum starvation, the expression of Jab1, phosphor-Akt (p-Akt) was up-regulated, whereas BRSK1 and p27(Kip1) were decreased.
Furthermore, we identified high expression of FOXA1 in breast cancer cell lines and tissues, discovered a role for BRCA1 in the regulation of p27(Kip1) transcription and a possible interaction with BRCA1.
The cyclin-dependent kinase inhibitor p27 (Kip1) is an important cell cycle regulatory gene in breast cancer, and decreased p27 expression is associated with poor prognosis.
Among the miRNAs involved in breast cancer, miR-221 plays a crucial role for the following reasons: i) miR-221 is significantly overexpressed in triple-negative primary breast cancer; ii) the oncosuppressor p27Kip1, a validated miR-221 target is downregulated in aggressive cancer cell lines; and iii) the upregulation of a key transcription factor, Slug, appears to be crucial, since it binds to the miR-221/miR-222 promoter and is responsible for the high expression of the miR-221/miR-222 cluster in breast cancer cells.
In epithelial cells of normal and benign breast disease, expression of p27Kip1 was well preserved while its expression markedly decreased in breast cancer (45 of 68).
Based on this meta-analysis, we conclude that the cyclin-dependent kinase inhibitor 1Brs2066827 polymorphism might not be a risk factor for breast cancer development.
Through pharmacologic approaches, we demonstrated that SRC and PKC negatively regulated expression of the cell-cycle inhibitor protein p27KIP1, and are necessary for CCL2-induced breast cancer cell proliferation.
The purpose is to evaluate expression levels of Jun activation domain-binding protein 1 (JAB1) in breast cancer tissue and adjacent normal tissue, to determine whether JAB1 expression is associated with p27(Kip1) expression in invasive breast carcinomas, and to evaluate the prognostic significance of JAB1 and p27(Kip1) in node-negative breast cancer.
Therefore, the data reported here demonstrate that miR-24-3p is an important regulator in breast cancer, and imply that the miR-24-3p/p27Kip1 axis has potential as a therapeutic target for breast cancer.
Moreover, we demonstrated that the anti-proliferative effect of silencing Sam68 on breast cancer cells was associated with up-regulation of cyclin-dependent kinase inhibitor p21(Cip1) and p27(Kip1), enhanced transactivation of FOXO factors, and attenuation of Akt/GSK-3β signalling.