Role of Cks1 amplification and overexpression in breast cancer.
Gain of chromosome 1q is a common event in many kinds of carcinomas. The Cks1 gene, located at 1q21, is required for p27 ubiquitination by the SCF(skp2) ubiquitinating machinery. In the present study, we found that Cks1 gene amplification was highly correlated with protein overexpression. Statistical analysis showed that amplification and overexpression of Cks1 were strongly associated with lymph node metastasis and poor prognosis. At the molecular level, knockdown of Cks1 expression by RNA interference inhibited the growth of MDA-MB-231 cells, damaged cell migration and invasion ability. Knockdown of Cks1 expression promoted apoptosis of breast cancer cells and a wobble mutant of Cks1 that was resistant to Cks1 siRNA can rescue this effect. Overexpression of Cks1 inhibited the apoptosis of breast cancer cells through the MEK-Erk pathway. These data suggest that Cks1 is an oncogene in the 1q21 amplicon and plays an important role for breast cancer development.
Wang
Xiao-Chun
XC
Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Science, Tianjin 300192, China.
Tian
Jing
J
Tian
Li-Li
LL
Wu
Hai-Liang
HL
Meng
Ai-min
AM
Ma
Ting-Hang
TH
Xiao
Jun
J
Xiao
Xiu-Ling
XL
Li
Chun-Hua
CH
D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness; D009857:Oncogenes; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured
C093090:CKS1B protein, human; D002352:Carrier Proteins; D034741:RNA, Small Interfering; D042846:CDC2-CDC28 Kinases; D018844:Cyclin-Dependent Kinases