PMID- 21258428
OWN - NLM
STAT- MEDLINE
DCOM- 20111121
LR  - 20211020
IS  - 1868-8500 (Electronic)
IS  - 1868-8497 (Print)
IS  - 1868-8497 (Linking)
VI  - 1
IP  - 5
DP  - 2010 Oct
TI  - Amphiregulin mediates estrogen, progesterone, and EGFR signaling in the normal 
      rat mammary gland and in hormone-dependent rat mammary cancers.
PG  - 229-44
LID - 10.1007/s12672-010-0048-0 [doi]
AB  - Both estrogen (E) and progesterone (P) are implicated in the etiology of human 
      breast cancer. Defining their mechanisms of action, particularly in vivo, is 
      relevant to the prevention and therapy of breast cancer. We investigated the 
      molecular and cellular mechanisms of E and/or P-induced in vivo proliferation, in 
      the normal rat mammary gland and in hormone-dependent rat mammary cancers which 
      share many characteristics with the normal human breast and hormone-dependent 
      breast cancers. We show that E+P treatment induced significantly greater 
      proliferation in both the normal gland and mammary cancers compared to E alone. 
      In both the normal gland and tumors, E+P-induced proliferation was mediated 
      through the increased production of amphiregulin (Areg), an epidermal growth 
      factor receptor (EGFR) ligand, and the activation of intracellular signaling 
      pathways (Erk, Akt, JNK) downstream of EGFR that regulate proliferation. In vitro 
      experiments using rat primary mammary organoids or T47D breast cancer cells 
      confirmed that Areg and the synthetic progestin, R5020, synergize to promote cell 
      proliferation through EGFR signaling. Iressa, an EGFR inhibitor, effectively 
      blocked this proliferation. These results indicate that mediators of cross talk 
      between E, P, and EGFR pathways may be considered as relevant molecular targets 
      for the therapy of hormone-dependent breast cancers, especially in premenopausal 
      women.
CI  - (c) The Author(s) 2010. This article is published with open access at 
      Springerlink.com.
FAU - Kariagina, Anastasia
AU  - Kariagina A
AD  - Department of Physiology, Breast Cancer and the Environment Research Center, 
      Michigan State University, 2201 Biomedical & Physical Sciences Bldg, East 
      Lansing, MI, USA.
FAU - Xie, Jianwei
AU  - Xie J
FAU - Leipprandt, Jeffrey R
AU  - Leipprandt JR
FAU - Haslam, Sandra Z
AU  - Haslam SZ
LA  - eng
GR  - U01 ES012800/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20101123
PL  - United States
TA  - Horm Cancer
JT  - Hormones & cancer
JID - 101518427
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Areg protein, rat)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Estrogens)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Amphiregulin
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - EGF Family of Proteins
MH  - ErbB Receptors/*metabolism
MH  - Estrogens/*metabolism
MH  - Female
MH  - Gene Expression Regulation/physiology
MH  - Glycoproteins/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Mammary Glands, Animal/metabolism
MH  - Mammary Neoplasms, Experimental/*metabolism
MH  - Neoplasms, Hormone-Dependent/metabolism
MH  - Progesterone/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*physiology
PMC - PMC3000471
COIS- The authors declare that they have no conflict of interests.
EDAT- 2011/01/25 06:00
MHDA- 2011/12/13 00:00
PMCR- 2010/11/23
CRDT- 2011/01/25 06:00
PHST- 2011/01/25 06:00 [entrez]
PHST- 2011/01/25 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2010/11/23 00:00 [pmc-release]
AID - 48 [pii]
AID - 10.1007/s12672-010-0048-0 [doi]
PST - ppublish
SO  - Horm Cancer. 2010 Oct;1(5):229-44. doi: 10.1007/s12672-010-0048-0. Epub 2010 Nov 
      23.