Skp2 is over-expressed in breast cancer and promotes breast cancer cell proliferation.
The F box protein Skp2 is oncogenic. Skp2 and Skp2B, an isoform of Skp2 are overexpressed in breast cancer. However, little is known regarding the mechanism by which Skp2B promotes the occurrence and development of breast cancer. Here, we determined the expression and clinical outcomes of Skp2 in breast cancer samples and cell lines using breast cancer database, and investigated the role of Skp2 and Skp2B in breast cancer cell growth, apoptosis and cell cycle arrest. We obtained Skp2 is significantly overexpressed in breast cancer samples and cell lines, and high Skp2 expression positively correlated with poor prognosis of breast cancer. Both Skp2 and Skp2B could promote breast cancer cell proliferation, inhibit cell apoptosis, change the cell cycle distribution and induce the increased S phase cells and therefore induce cell proliferation in breast cancer cells. Moreover, the 2 isoforms could both suppress PIG3 expression via independent pathways in the breast cancer cells. Skp2 suppressed p53 and inhibited PIG3-induced apoptosis, while Skp2B attenuated the function of PIG3 by inhibiting PHB. Our results indicate that Skp2 and Skp2B induce breast cancer cell development and progression, making Skp2 and Skp2B potential molecular targets for breast cancer therapy.
a Department of Medical Oncology , Jinling Hospital , Medical School of Nanjing University , Nanjing , China.
Wenwen
W
Zhang
a Department of Medical Oncology , Jinling Hospital , Medical School of Nanjing University , Nanjing , China.
Lulu
L
Cao
a Department of Medical Oncology , Jinling Hospital , Medical School of Nanjing University , Nanjing , China.
Zijia
Z
Sun
a Department of Medical Oncology , Jinling Hospital , Medical School of Nanjing University , Nanjing , China.
Jing
J
Xu
a Department of Medical Oncology , Jinling Hospital , Medical School of Nanjing University , Nanjing , China.
Lin
L
Tang
a Department of Medical Oncology , Jinling Hospital , Medical School of Nanjing University , Nanjing , China.
Weiwei
W
Chen
a Department of Medical Oncology , Jinling Hospital , Medical School of Nanjing University , Nanjing , China.
Jiayan
J
Luo
a Department of Medical Oncology , Jinling Hospital , Medical School of Nanjing University , Nanjing , China.
Fang
F
Yang
b Department of Medicine ; Rutgers New Jersey Medical School , Newark , NJ , USA.
Yucai
Y
Wang
a Department of Medical Oncology , Jinling Hospital , Medical School of Nanjing University , Nanjing , China.|c Department of Medical Oncology, Jinling Hospital, Nanjing Medical University, Nanjing, China.
Xiaoxiang
X
Guan
D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016208:Databases, Factual; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D011379:Prognosis; D000091402:Prohibitins; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; C000717328:PHB protein, human; D000091402:Prohibitins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D044786:S-Phase Kinase-Associated Proteins; C495901:TP53 protein, human; C411296:TP53I3 protein, human; D016159:Tumor Suppressor Protein p53
PHB; PIG3; Skp2; Skp2B; breast cancer; p53; prognosis; proliferation