PMID- 20953835
OWN - NLM
STAT- MEDLINE
DCOM- 20120913
LR  - 20211203
IS  - 1573-7217 (Electronic)
IS  - 0167-6806 (Linking)
VI  - 128
IP  - 3
DP  - 2011 Aug
TI  - Clinical potential of the mTOR targets S6K1 and S6K2 in breast cancer.
PG  - 713-23
LID - 10.1007/s10549-010-1058-x [doi]
AB  - The mammalian target of rapamycin (mTOR) and its substrates S6K1 and S6K2 
      regulate cell growth, proliferation, and metabolism through translational 
      control. RPS6KB1 (S6K1) and RPS6KB2 (S6K2) are situated in the commonly amplified 
      17q21-23 and 11q13 regions. S6K1 amplification and protein overexpression have 
      earlier been associated with a worse outcome in breast cancer, but information 
      regarding S6K2 is scarce. The aim of this study was to evaluate the prognostic 
      and treatment predictive relevance of S6K1/S6K2 gene amplification, as well as 
      S6K2 protein expression in breast cancer. S6K1/S6K2 gene copy number was 
      determined by real-time PCR in 207 stage II breast tumors and S6K2 protein 
      expression was investigated by immunohistochemistry in 792 node-negative breast 
      cancers. S6K1 amplification/gain was detected in 10.7%/21.4% and S6K2 
      amplification/gain in 4.3%/21.3% of the tumors. S6K2 protein was detected in the 
      nucleus (38%) and cytoplasm (76%) of the tumor cells. S6K1 amplification was 
      significantly associated with HER2 gene amplification and protein expression. 
      S6K2 amplification correlated significantly with high S6K2 mRNA levels, ER+ 
      status and CCND1 amplification. S6K1 and S6K2 gene amplification was associated 
      with a worse prognosis independent of HER2 and CCND1. S6K2 gain and nuclear S6K2 
      expression was related to an improved benefit from tamoxifen among patients with 
      ER+, respectively ER+/PgR+ tumors. In the ER+/PgR- subgroup, nuclear S6K2 rather 
      indicated decreased tamoxifen responsiveness. S6K1 amplification predicted 
      reduced benefit from radiotherapy. This is the first study showing that S6K2 
      amplification and overexpression, like S6K1 amplification, have prognostic and 
      treatment predictive significance in breast cancer.
FAU - Perez-Tenorio, Gizeh
AU  - Perez-Tenorio G
AD  - Department of Clinical and Experimental Medicine, Linkoping University, 
      Linkoping, Sweden.
FAU - Karlsson, Elin
AU  - Karlsson E
FAU - Waltersson, Marie Ahnstrom
AU  - Waltersson MA
FAU - Olsson, Birgit
AU  - Olsson B
FAU - Holmlund, Birgitta
AU  - Holmlund B
FAU - Nordenskjold, Bo
AU  - Nordenskjold B
FAU - Fornander, Tommy
AU  - Fornander T
FAU - Skoog, Lambert
AU  - Skoog L
FAU - Stal, Olle
AU  - Stal O
LA  - eng
PT  - Journal Article
DEP - 20101016
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - Breast Cancer Res Treat. 2011 Aug;128(3):607-11. PMID: 20953834
MH  - Breast Neoplasms/diagnosis/*enzymology/genetics/mortality/pathology
MH  - DNA Copy Number Variations
MH  - Female
MH  - Gene Amplification/genetics
MH  - Humans
MH  - Prognosis
MH  - Recurrence
MH  - Ribosomal Protein S6 Kinases, 70-kDa/genetics/*metabolism
MH  - Survival Analysis
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2010/10/19 06:00
MHDA- 2012/09/14 06:00
CRDT- 2010/10/19 06:00
PHST- 2010/03/25 00:00 [received]
PHST- 2010/07/08 00:00 [accepted]
PHST- 2010/10/19 06:00 [entrez]
PHST- 2010/10/19 06:00 [pubmed]
PHST- 2012/09/14 06:00 [medline]
AID - 10.1007/s10549-010-1058-x [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2011 Aug;128(3):713-23. doi: 10.1007/s10549-010-1058-x. 
      Epub 2010 Oct 16.