Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0338671 (
Steroids
)
9,479
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Estrogen receptor-negative breast carcinomas are more aggressive and are unresponsive to anti-estrogens. Thus, they clearly require new therapies targeted against specific genes and proteins actively engaged in the pathophysiology of cancer. The S-phase kinase-associated protein
Skp2
is required for the ubiquitin-mediated degradation of the cdk-inhibitor p27 and is a bona fide proto-oncoprotein. We attempted to explore whether
Skp2
may be a potential specific therapeutic target in the subset of aggressive breast carcinomas by investigating the possible relationship between expression of
Skp2
and p27 proteins and estrogen receptor (ER). Immunohistochemical analysis of tumor tissues was employed to determine the expression of
Skp2
, p27, and ER proteins in 82 cases of primary breast carcinoma. Higher levels of
Skp2
were detected more frequently in ER-negative tumors and tumors metastatic to the axillary lymph nodes. The expression of p27 was inverse with the histologic grade. Statistical analysis showed that the percentage of high
Skp2
expressors was significantly greater in the group with low p27 expression than in the group with high p27 expression. The current study, together with the results from a previous study, demonstrated the existence of a subtype of high-grade, negative ER breast carcinomas with high
Skp2
and low p27 levels. This implies that
Skp2
may be a potential specific therapeutic target in a subset of aggressive breast carcinomas. Thus far, there is no specific therapy for the ER-negative and HER-2/neu resistant groups, which are among the subset of aggressive tumors.
Steroids
2005 Oct
PMID:Relationship between levels of Skp2 and P27 in breast carcinomas and possible role of Skp2 as targeted therapy. 1602 59