PMID- 25694511
OWN - NLM
STAT- MEDLINE
DCOM- 20151201
LR  - 20181113
IS  - 1479-6821 (Electronic)
IS  - 1351-0088 (Print)
IS  - 1351-0088 (Linking)
VI  - 22
IP  - 2
DP  - 2015 Apr
TI  - Highly specific role of the insulin receptor in breast cancer progression.
PG  - 145-57
LID - 10.1530/ERC-14-0490 [doi]
AB  - Accumulating evidence from clinical trials indicates that specific targeting of 
      the IGF1 receptor (IGF1R) is not efficient as an anti-breast cancer treatment. 
      One possible reason is that the mitogenic signals from the insulin receptor (IR) 
      can be processed independently or as compensation to inhibition of the IGF1R. In 
      this study, we highlight the role of the IR in mediating breast tumor progression 
      in both WT mice and a hyperinsulinemic MKR mouse model by induction of Ir (Insr) 
      or Igf1r knockdown (KD) in the mammary carcinoma Mvt-1 cell line. By using the 
      specific IR antagonist-S961, we demonstrated that Igf1r-KD induces elevated 
      responses by the IR to IGF1. On the other hand, Ir-KD cells generated 
      significantly smaller tumors in the mammary fat pads of both WT and MKR mice, as 
      opposed to control cells, whereas the Igf1r-KD cells did not. The tumorigenic 
      effects of insulin on the Mvt-1 cells were also demonstrated using microarray 
      analysis, which indicates alteration of genes and signaling pathways involved in 
      proliferation, the cell cycle, and apoptosis following insulin stimulation. In 
      addition, the correlation between IR and the potential prognostic marker for 
      aggressive breast cancer, CD24, was examined in the Ir-KD cells. 
      Fluorescence-activated cell sorting (FACS) analysis revealed more than 60% 
      reduction in CD24 expression in the Ir-KD cells when compared with the control 
      cells. Our results also indicate that CD24-expressing cells can restore, at least 
      in part, the tumorigenic capacity of Ir-KD cells. Taken together, our results 
      highlight the mitogenic role of the IR in mammary tumor progression with a direct 
      link to CD24 expression.
CI  - (c) 2015 Society for Endocrinology.
FAU - Rostoker, Ran
AU  - Rostoker R
AD  - Clinical Research Institute at Rambam (CRIR) and the Faculty of MedicineTechnion, 
      Diabetes and Metabolism Clinical Research Center of Excellence, Haifa, IsraelThe 
      Laboratory of Molecular MedicineRambam Health Care Campus and Rappaport Faculty 
      of Medicine and Research Institute, Technion, Haifa 31096, IsraelDivision of 
      EndocrinologyDiabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Abelson, Sagi
AU  - Abelson S
AD  - Clinical Research Institute at Rambam (CRIR) and the Faculty of MedicineTechnion, 
      Diabetes and Metabolism Clinical Research Center of Excellence, Haifa, IsraelThe 
      Laboratory of Molecular MedicineRambam Health Care Campus and Rappaport Faculty 
      of Medicine and Research Institute, Technion, Haifa 31096, IsraelDivision of 
      EndocrinologyDiabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Bitton-Worms, Keren
AU  - Bitton-Worms K
AD  - Clinical Research Institute at Rambam (CRIR) and the Faculty of MedicineTechnion, 
      Diabetes and Metabolism Clinical Research Center of Excellence, Haifa, IsraelThe 
      Laboratory of Molecular MedicineRambam Health Care Campus and Rappaport Faculty 
      of Medicine and Research Institute, Technion, Haifa 31096, IsraelDivision of 
      EndocrinologyDiabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Genkin, Inna
AU  - Genkin I
AD  - Clinical Research Institute at Rambam (CRIR) and the Faculty of MedicineTechnion, 
      Diabetes and Metabolism Clinical Research Center of Excellence, Haifa, IsraelThe 
      Laboratory of Molecular MedicineRambam Health Care Campus and Rappaport Faculty 
      of Medicine and Research Institute, Technion, Haifa 31096, IsraelDivision of 
      EndocrinologyDiabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Ben-Shmuel, Sarit
AU  - Ben-Shmuel S
AD  - Clinical Research Institute at Rambam (CRIR) and the Faculty of MedicineTechnion, 
      Diabetes and Metabolism Clinical Research Center of Excellence, Haifa, IsraelThe 
      Laboratory of Molecular MedicineRambam Health Care Campus and Rappaport Faculty 
      of Medicine and Research Institute, Technion, Haifa 31096, IsraelDivision of 
      EndocrinologyDiabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Dakwar, Maria
AU  - Dakwar M
AD  - Clinical Research Institute at Rambam (CRIR) and the Faculty of MedicineTechnion, 
      Diabetes and Metabolism Clinical Research Center of Excellence, Haifa, IsraelThe 
      Laboratory of Molecular MedicineRambam Health Care Campus and Rappaport Faculty 
      of Medicine and Research Institute, Technion, Haifa 31096, IsraelDivision of 
      EndocrinologyDiabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Orr, Zila Shen
AU  - Orr ZS
AD  - Clinical Research Institute at Rambam (CRIR) and the Faculty of MedicineTechnion, 
      Diabetes and Metabolism Clinical Research Center of Excellence, Haifa, IsraelThe 
      Laboratory of Molecular MedicineRambam Health Care Campus and Rappaport Faculty 
      of Medicine and Research Institute, Technion, Haifa 31096, IsraelDivision of 
      EndocrinologyDiabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Caspi, Avishay
AU  - Caspi A
AD  - Clinical Research Institute at Rambam (CRIR) and the Faculty of MedicineTechnion, 
      Diabetes and Metabolism Clinical Research Center of Excellence, Haifa, IsraelThe 
      Laboratory of Molecular MedicineRambam Health Care Campus and Rappaport Faculty 
      of Medicine and Research Institute, Technion, Haifa 31096, IsraelDivision of 
      EndocrinologyDiabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - Tzukerman, Maty
AU  - Tzukerman M
AD  - Clinical Research Institute at Rambam (CRIR) and the Faculty of MedicineTechnion, 
      Diabetes and Metabolism Clinical Research Center of Excellence, Haifa, IsraelThe 
      Laboratory of Molecular MedicineRambam Health Care Campus and Rappaport Faculty 
      of Medicine and Research Institute, Technion, Haifa 31096, IsraelDivision of 
      EndocrinologyDiabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA.
FAU - LeRoith, Derek
AU  - LeRoith D
AD  - Clinical Research Institute at Rambam (CRIR) and the Faculty of MedicineTechnion, 
      Diabetes and Metabolism Clinical Research Center of Excellence, Haifa, IsraelThe 
      Laboratory of Molecular MedicineRambam Health Care Campus and Rappaport Faculty 
      of Medicine and Research Institute, Technion, Haifa 31096, IsraelDivision of 
      EndocrinologyDiabetes and Bone Diseases, Icahn School of Medicine at Mount Sinai, 
      New York City, New York, USA Clinical Research Institute at Rambam (CRIR) and the 
      Faculty of MedicineTechnion, Diabetes and Metabolism Clinical Research Center of 
      Excellence, Haifa, IsraelThe Laboratory of Molecular MedicineRambam Health Care 
      Campus and Rappaport Faculty of Medicine and Research Institute, Technion, Haifa 
      31096, IsraelDivision of EndocrinologyDiabetes and Bone Diseases, Icahn School of 
      Medicine at Mount Sinai, New York City, New York, USA 
      d_leroith@rambam.health.gov.il.
LA  - eng
GR  - R01 CA128799/CA/NCI NIH HHS/United States
GR  - 2R01CA128799-06A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (CD24 Antigen)
RN  - 0 (Cd24a protein, mouse)
RN  - 0 (Insulin)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - CD24 Antigen/metabolism
MH  - Cell Line, Tumor
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Insulin/pharmacology
MH  - Mammary Neoplasms, Animal/*metabolism/pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptor, IGF Type 1/metabolism
MH  - Receptor, Insulin/*metabolism
MH  - Signal Transduction
MH  - Tumor Burden
PMC - PMC4362669
MID - NIHMS660610
OTO - NOTNLM
OT  - breast cancer and CD24
OT  - hyperinsulinemia
OT  - insulin receptor
OT  - insulin-like growth factor 1 receptor
EDAT- 2015/02/20 06:00
MHDA- 2015/12/15 06:00
PMCR- 2015/04/01
CRDT- 2015/02/20 06:00
PHST- 2015/02/20 06:00 [entrez]
PHST- 2015/02/20 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - 22/2/145 [pii]
AID - 10.1530/ERC-14-0490 [doi]
PST - ppublish
SO  - Endocr Relat Cancer. 2015 Apr;22(2):145-57. doi: 10.1530/ERC-14-0490.