Oncogenic role of Skp2 and p27Kip1 in intraductal proliferative lesions of the breast.
OBJECTIVE
To investigate whether the connection of p27(Kip1) to S-phase kinase-associated protein 2 (Skp2) plays an oncogenic role in intraductal proliferative lesions of the breast.


METHODS
Here we investigated the mechanism involved in association of Skp2’s degradation of p27(Kip1) with the breast carcinogenesis by immunohistochemical method through detection of Skp2 and p27(Kip1) protein levels in 120 paraffin-embedded tissues of intraductal proliferative lesions including usual ductal hyperplasia (UDH, n=30), atypical ductal hyperplasia (n=30), flat epithelial atypia (FEA, n=30), and ductal carcinoma in situ (DCIS, n=30). Moreover, the expression status of Skp2 and p27(Kip1) in 30 cases of the normal breast paraffin-embedded tissues were explored.


RESULTS
The DCIS group was with the highest Skp2 level and the lowest p27(Kip1) level, and the UDH group was with the lowest Skp2 level and the highest p27(Kip1) level.Both Skp2 and p27(Kip1) levels in the DCIS group were significantly different from those in the UDH group (all P<0.01).The levels of Skp2 and p27(Kip1) in the FEA group were significantly different from both the DCIS and UDH groups (all P<0.05).p27(Kip1) was negatively correlated with Skp2 in both the UDH group (r=-0.629, P=0.026) and DCIS group (r=-0.893, P=0.000).


CONCLUSIONS
Overexpression of Skp2 might be the mechanism underlying p27(Kip1) over degradation.
Department of Acupuncture and Moxibustion, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. lvyanella@163.com
Lv
L
Yan
Niu
N
Yun
Ding
D
Xiu-Min
Xiao
X
Xu-Qi
D000328:Adult; D000368:Aged; D001940:Breast / Q000473:pathology*; D001943:Breast Neoplasms / Q000209:etiology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000209:etiology*; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000502:physiology*; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008875:Middle Aged; D044786:S-Phase Kinase-Associated Proteins / Q000502:physiology*
C436291:CDKN1B protein, human; D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27