PMID- 24127567
OWN - NLM
STAT- MEDLINE
DCOM- 20140804
LR  - 20211209
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Print)
IS  - 0021-9533 (Linking)
VI  - 126
IP  - Pt 24
DP  - 2013 Dec 15
TI  - Insulin receptor isoform switching in intestinal stem cells, progenitors, 
      differentiated lineages and tumors: evidence that IR-B limits proliferation.
PG  - 5645-56
LID - 10.1242/jcs.132985 [doi]
AB  - Despite evidence for the impact of insulin on intestinal epithelial physiology 
      and pathophysiology, the expression patterns, roles, and regulation of insulin 
      receptor (IR) and IR isoforms in the intestinal epithelium are not well 
      characterized. IR-A is thought to mediate the proliferative effects of insulin or 
      insulin growth factors (IGFs) in fetal or cancer cells. IR-B is considered to be 
      the metabolic receptor for insulin in specialized tissues. This study used a 
      novel Sox9-EGFP reporter mouse that permits isolation of intestinal epithelial 
      stem cells (IESCs), progenitors, enteroendocrine cells and differentiated 
      lineages, the Apc(Min/+) mouse model of precancerous adenoma and normal human 
      intestinal and colorectal cancer (CRC) cell lines. We tested the hypothesis that 
      there is differential expression of IR-A or IR-B in stem and tumor cells versus 
      differentiated intestinal epithelial cells (IECs) and that IR-B impacts cell 
      proliferation. Our findings provide evidence that IR-B expression is 
      significantly lower in highly proliferative IESCs and progenitor cells versus 
      post-mitotic, differentiated IECs and in subconfluent and undifferentiated versus 
      differentiated Caco-2 cells. IR-B is also reduced in Apc(Min/+) tumors and highly 
      tumorigenic CRC cells. These differences in IR-B were accompanied by altered 
      levels of mRNAs encoding muscleblind-like 2 (MBNL2), a known regulator of IR 
      alternative splicing. Forced IR-B expression in subconfluent and undifferentiated 
      Caco-2 cells reduced proliferation and increased biomarkers of differentiation. 
      Our findings indicate that the impact of insulin on different cell types in the 
      intestinal epithelium might differ depending on relative IR-B IR-A expression 
      levels and provide new evidence for the roles of IR-B to limit proliferation of 
      CRC cells.
FAU - Andres, Sarah F
AU  - Andres SF
AD  - Department of Cell Biology and Physiology, University of North Carolina at Chapel 
      Hill, Chapel Hill, NC 27599, USA.
FAU - Simmons, James G
AU  - Simmons JG
FAU - Mah, Amanda T
AU  - Mah AT
FAU - Santoro, M Agostina
AU  - Santoro MA
FAU - Van Landeghem, Laurianne
AU  - Van Landeghem L
FAU - Lund, P Kay
AU  - Lund PK
LA  - eng
GR  - 5-R01-DK040247-19/DK/NIDDK NIH HHS/United States
GR  - P30 DK034987/DK/NIDDK NIH HHS/United States
GR  - F31-AG040943/AG/NIA NIH HHS/United States
GR  - R01 DK040247/DK/NIDDK NIH HHS/United States
GR  - P30-DK034987/DK/NIDDK NIH HHS/United States
GR  - F31 AG040943/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131014
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Protein Isoforms)
RN  - 0 (TJP1 protein, human)
RN  - 0 (Zonula Occludens-1 Protein)
RN  - 0 (beta Catenin)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Animals
MH  - Caco-2 Cells
MH  - Cell Differentiation
MH  - *Cell Proliferation
MH  - Colorectal Neoplasms/*metabolism
MH  - DNA Replication
MH  - Gene Expression
MH  - Humans
MH  - Intestinal Mucosa/metabolism
MH  - Mice
MH  - Phenotype
MH  - Protein Isoforms/genetics/metabolism
MH  - Receptor, Insulin/genetics/*metabolism
MH  - Signal Transduction
MH  - Stem Cells/*metabolism
MH  - Zonula Occludens-1 Protein/metabolism
MH  - beta Catenin/metabolism
PMC - PMC3860310
OTO - NOTNLM
OT  - Colon cancer
OT  - Differentiation
OT  - Insulin receptor isoform B
OT  - Intestinal stem cell
OT  - Proliferation
EDAT- 2013/10/16 06:00
MHDA- 2014/08/05 06:00
PMCR- 2014/12/15
CRDT- 2013/10/16 06:00
PHST- 2013/10/16 06:00 [entrez]
PHST- 2013/10/16 06:00 [pubmed]
PHST- 2014/08/05 06:00 [medline]
PHST- 2014/12/15 00:00 [pmc-release]
AID - jcs.132985 [pii]
AID - 10.1242/jcs.132985 [doi]
PST - ppublish
SO  - J Cell Sci. 2013 Dec 15;126(Pt 24):5645-56. doi: 10.1242/jcs.132985. Epub 2013 
      Oct 14.