PMID- 19903848
OWN - NLM
STAT- MEDLINE
DCOM- 20091221
LR  - 20131121
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 69
IP  - 23
DP  - 2009 Dec 1
TI  - Estradiol alters cell growth in nonmalignant colonocytes and reduces the 
      formation of preneoplastic lesions in the colon.
PG  - 9118-24
LID - 10.1158/0008-5472.CAN-09-2348 [doi]
AB  - Numerous clinical and animal studies show that hormone replacement therapy 
      reduces the risk of colon tumor formation. However, the majority of experiments 
      have shown that estradiol (E(2)) does not inhibit the growth of malignantly 
      transformed colon epithelia. As such, the presented studies focused on evaluating 
      the effects of E(2) in noncancerous colonocytes. E(2) treatments (0-10 nmol/L) 
      reduced cell growth and increased apoptotic activity in young adult mouse 
      colonocytes (YAMC), a nonmalignant cell line, in a dose-responsive manner. These 
      effects were lost in the YAMC-Ras cells, an isogenic cell line with a single 
      malignant transformation. Cotreatment with an estrogen receptor (ER) antagonist 
      inhibited the physiologic effects of E(2) in YAMC cells, suggesting that the 
      response is ER mediated. To further study the effect of E(2) on colonic 
      epithelia, we evaluated the development of preneoplastic lesions in 
      ovariectomized wild-type (WT) and ERbeta knockout (ERbetaKO) mice treated with 
      either vehicle or E(2). WT E(2)-treated animals exhibited significantly fewer 
      aberrant crypt foci and increased apoptotic activity in colonic epithelia when 
      compared with WT control mice or ERbetaKO animals receiving either treatment. For 
      the first time, we showed that E(2) alters the growth of nontransformed 
      colonocytes in vitro and that, through an ERbeta-mediated mechanism, E(2) 
      influences the physiology of noncancerous colonocytes, resulting in fewer 
      preneoplastic lesions. Collectively, these data show that the protective actions 
      of E(2) occur primarily during the initiation/promotion stages of disease 
      development and identify the hormone as an important chemoprotective agent.
FAU - Weige, Charles C
AU  - Weige CC
AD  - Genetics Interdisciplinary Program, Texas A&M University, College Station, Texas 
      77843, USA.
FAU - Allred, Kimberly F
AU  - Allred KF
FAU - Allred, Clinton D
AU  - Allred CD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091110
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Estrogen Receptor beta)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Cell Growth Processes/drug effects/physiology
MH  - Colon/cytology/*drug effects/metabolism
MH  - Colonic Neoplasms/genetics/metabolism/pathology/*prevention & control
MH  - Dose-Response Relationship, Drug
MH  - Estradiol/blood/*pharmacology
MH  - Estrogen Receptor beta/biosynthesis
MH  - Female
MH  - Genes, ras
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Precancerous Conditions/genetics/metabolism/pathology/*prevention & control
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2009/11/12 06:00
MHDA- 2009/12/22 06:00
CRDT- 2009/11/12 06:00
PHST- 2009/11/12 06:00 [entrez]
PHST- 2009/11/12 06:00 [pubmed]
PHST- 2009/12/22 06:00 [medline]
AID - 0008-5472.CAN-09-2348 [pii]
AID - 10.1158/0008-5472.CAN-09-2348 [doi]
PST - ppublish
SO  - Cancer Res. 2009 Dec 1;69(23):9118-24. doi: 10.1158/0008-5472.CAN-09-2348. Epub 
      2009 Nov 10.