PMID- 25904072
OWN - NLM
STAT- MEDLINE
DCOM- 20160216
LR  - 20150527
IS  - 1521-6551 (Electronic)
IS  - 1521-6543 (Linking)
VI  - 67
IP  - 4
DP  - 2015 Apr
TI  - Involvement of Different networks in mammary gland involution after the 
      pregnancy/lactation cycle: Implications in breast cancer.
PG  - 227-38
LID - 10.1002/iub.1365 [doi]
AB  - Early pregnancy is associated with a reduction in a woman's lifetime risk for 
      breast cancer. However, different studies have demonstrated an increase in breast 
      cancer risk in the years immediately following pregnancy. Early and long-term 
      risk is even higher if the mother age is above 35 years at the time of first 
      parity. The proinflammatory microenvironment within the mammary gland after 
      pregnancy renders an "ideal niche" for oncogenic events. Signaling pathways 
      involved in programmed cell death and tissue remodeling during involution are 
      also activated in breast cancer. Herein, the major signaling pathways involved in 
      mammary gland involution, signal transducer and activator of transcription 
      (STAT3), nuclear factor-kappa B (NF-kappaB), transforming growth factor beta (TGFbeta), 
      and retinoid acid receptors (RARs)/retinoid X receptors (RXRs), are reviewed as 
      part of the complex network of signaling pathways that crosstalk in a 
      contextual-dependent manner. These factors, also involved in breast cancer 
      development, are important regulatory nodes for signaling amplification after 
      weaning. Indeed, during involution, p65/p300 target genes such as MMP9, Capn1, 
      and Capn2 are upregulated. Elevated expression and activities of these proteases 
      in breast cancer have been extensively documented. The role of these proteases 
      during mammary gland involution is further discussed. MMPs, calpains, and 
      cathepsins exert their effect by modification of the extracellular matrix and 
      intracellular proteins. Calpains, activated in the mammary gland during 
      involution, cleave several proteins located in cell membrane, lysosomes, 
      mitochondria, and nuclei favoring cell death. Besides, during this period, Capn1 
      is most probably involved in the modulation of preadipocyte differentiation 
      through chromatin remodeling. Calpains can be implicated in cell anchoring loss, 
      providing a proper microenvironment for tumor growth. A better understanding of 
      the role of any of these proteases in tumorigenesis may yield novel therapeutic 
      targets or prognostic markers for breast cancer.
CI  - (c) 2015 International Union of Biochemistry and Molecular Biology.
FAU - Zaragoza, Rosa
AU  - Zaragoza R
AD  - Instituto INCLIVA, Facultad de Medicina/Hospital Clinico, Universidad de 
      Valencia, Valencia, Spain.
FAU - Garcia-Trevijano, Elena R
AU  - Garcia-Trevijano ER
AD  - Instituto INCLIVA, Facultad de Medicina/Hospital Clinico, Universidad de 
      Valencia, Valencia, Spain.
AD  - Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, 
      Universidad de Valencia, Valencia, Spain.
FAU - Lluch, Ana
AU  - Lluch A
AD  - Instituto INCLIVA, Facultad de Medicina/Hospital Clinico, Universidad de 
      Valencia, Valencia, Spain.
AD  - Servicio Oncologia Medica, Hospital Clinico Universitario Valencia, Valencia, 
      Spain.
FAU - Ribas, Gloria
AU  - Ribas G
AD  - Instituto INCLIVA, Facultad de Medicina/Hospital Clinico, Universidad de 
      Valencia, Valencia, Spain.
AD  - Servicio Oncologia Medica, Hospital Clinico Universitario Valencia, Valencia, 
      Spain.
FAU - Vina, Juan R
AU  - Vina JR
AD  - Instituto INCLIVA, Facultad de Medicina/Hospital Clinico, Universidad de 
      Valencia, Valencia, Spain.
AD  - Servicio Oncologia Medica, Hospital Clinico Universitario Valencia, Valencia, 
      Spain.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20150421
PL  - England
TA  - IUBMB Life
JT  - IUBMB life
JID - 100888706
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Breast Neoplasms/*pathology
MH  - Female
MH  - Humans
MH  - *Lactation
MH  - Mammary Glands, Human/*physiopathology
MH  - NF-kappa B/metabolism
MH  - Peptide Hydrolases/metabolism
MH  - Pregnancy
MH  - Risk Factors
MH  - Signal Transduction
MH  - Transcription Factors/metabolism
MH  - Transforming Growth Factor beta/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Calpains
OT  - NF-kappaB
OT  - STATs
OT  - Tissue remodeling
OT  - programmed cell death
EDAT- 2015/04/24 06:00
MHDA- 2016/02/18 06:00
CRDT- 2015/04/24 06:00
PHST- 2015/01/03 00:00 [received]
PHST- 2015/02/03 00:00 [accepted]
PHST- 2015/04/24 06:00 [entrez]
PHST- 2015/04/24 06:00 [pubmed]
PHST- 2016/02/18 06:00 [medline]
AID - 10.1002/iub.1365 [doi]
PST - ppublish
SO  - IUBMB Life. 2015 Apr;67(4):227-38. doi: 10.1002/iub.1365. Epub 2015 Apr 21.