Relationship between levels of Skp2 and P27 in breast carcinomas and possible role of Skp2 as targeted therapy.
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.
Zheng
Wei-qiang
WQ
Department of Pathology, Changhai Hospital, Second Military Medical University, 174 Chang-Hai Road, Shanghai 200433, China. zhengwq@hotmail.com
Zheng
Jian-ming
JM
Ma
Rong
R
Meng
Feng-fang
FF
Ni
Chan-rong
CR
D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000473:pathology; D002467:Cell Nucleus / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000032:analysis; D044786:S-Phase Kinase-Associated Proteins / Q000032:analysis* / Q000502:physiology; D017154:Stromal Cells / Q000737:chemistry
D011960:Receptors, Estrogen; D044786:S-Phase Kinase-Associated Proteins