We developed dual IHC staining for p27 and pY88, and found that benign breast epithelium was negative, while breast cancer biopsies (of varied hormonal status) could be stratified for pY88 status.
TOP2A, Ki67, and cyclin D1, as categorical variables were not predictive, whereas cyclin D1 as continuous variable was predictive of trastuzumab benefit.<b>Conclusions:</b> In TransHERA, patients with HER2-positive early breast cancer with low p27 expression in their tumors benefited from trastuzumab treatment, whereas patients with high p27 expression did not.<i></i>.
The use of ALT demonstrates that both CDK4 and CDK2 need to be inhibited if long-term efficacy is to be achieved and represents a novel modality to inhibit breast cancer cells.<b>Implications:</b> Modulating tyrosine phosphorylation of p27 impacts both proliferative (CDK4) and resistance (CDK2) mechanisms in breast cancer and suggests that phospho-p27 status may serve as a biomarker for patients that are responsive to CDK4/6 inhibition.<i></i>.
The objective of our study was to determine the association between expression of c-Myc and the loss of p27 by immunohistochemistry (IHC) in the four major subtypes of breast cancer (BC) (Luminal A, Luminal B, HER2, and Triple Negative) and with other clinicopathological factors in a population of 202 African-American (AA) women.
Cyclin E1, cyclin D1, p53, p21 and p27 were evaluated with immunohistochemistry in 1077 formalin-fixed paraffin-embedded tissues from breast cancer patients who had been treated within clinical trials.
Use of the triple-negative TMX2-28 breast cancer cell line to address the role of SKP2 in cell cycle progression confirmed that SKP2 contributes to a more rapid cell cycle progression and may regulates pSer10p27 levels.
While in vitro, following release of breast cancer cell lines from serum starvation, the expression of SKIP was up-regulated, whereas p27 was down-regulated.
The study demonstrates that the expression-enhancing regulatory variants of MCL1 are protective modifiers of breast cancer risk, and reduced cell proliferation and arrested cell cycle progression partly mediated by p27 might be the underlying mechanism.
This study provides preclinical evidence that combination of p21 (Waf1) and p27 (Kip1) could be a novel and promising therapeutic approach to treatment of breast cancer with suppressed p21 (Waf1) and p27 (Kip1) expression.
Our results suggest that tuberin and p27 are aberrantly expressed in malignant tissue, but their expression does not appear to be dependent on the BRCA mutation state of a breast cancer patient.
Curcumin, the main constituent of turmeric, has been found to stabilize p27 levels in breast cancer, but whether this effect is mediated through changes in Skp2 or Her2 expression remains unclear.
Interestingly, knocking down p21 or p27 individually did not alter As2O3-induced apoptosis and cell cycle arrest; however, the simultaneous down-regulation of both p21 and p27 resulted in attenuating of G1, G2/M arrest and reduction in apoptosis, thus indicating that p21 and p27 as the primary molecular targets of As2O3 against breast cancer.
In the present study, we found that erlotinib induces p27 phosphorylation at Ser¹⁰ (S10), and S10 p27 phosphorylation leads to erlotinib resistance in EGFR-expressing breast cancer.
Tumor levels of the cell cycle regulators cyclin E and p27 correlate strongly with survival in breast cancer patients and are specifically regulated by the ubiquitin ligases hCDC4 and SKP2.