PMID- 16899133
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20070724
LR  - 20200929
IS  - 1475-2867 (Electronic)
IS  - 1475-2867 (Linking)
VI  - 6
DP  - 2006 Aug 9
TI  - "Nutritional and chemopreventive anti-cancer agents up-regulate expression of 
      p27Kip1, a cyclin-dependent kinase inhibitor, in mouse JB6 epidermal and human 
      MCF7, MDA-MB-321 and AU565 breast cancer cells".
PG  - 20
AB  - BACKGROUND: p27(Kip1) is a cyclin-dependent kinase inhibitor. When up-regulated, 
      p27 inhibits G1-to-S phase transition of the cell cycle. This report addresses 
      the question of whether various nutritional and chemopreventive anti-cancer 
      agents up-regulate the expression of p27 in preneoplastic and neoplastic cells. 
      RESULTS: Experimental evidence presented in the first half of this report shows 
      that these agents fairly faithfully up-regulate expression of p27 in mouse 
      epidermal (JB6) and human breast cancer (MCF7, MDA-MB-321, and AU565) cells. 
      Up-regulation appears to be specific to p27 because expression of cyclin D1, E, 
      and A, and p21Cip1/Waf1 was not modulated by these agents. Up-regulation of the 
      expression of p27 is likely due to the activation of translation rather than 
      transcription of p27 because (a) up-regulation is mediated by the 5'-untranslated 
      region (-575) of the p27 gene and (b) the antibiotic actinomycin D, an inhibitor 
      of transcription, did not attenuate the up-regulation of p27. This latter finding 
      is likely to preclude the existence of cryptic transcription factor binding 
      site(s) in the 5'-untranslated region of p27 gene. The experimental evidence, 
      presented in the second half of this report, was obtained using the 
      5'-untranslated region (-575) of p27 gene. The evidence suggests that cancer 
      preventive agents up-regulate expression of p27 by at least four different 
      molecular signaling pathways: (a) Caloric restriction is likely to up-regulate 
      p27 expression via 5'-AMP-activated protein kinase (AMPK; a metabolic energy 
      sensor or cellular fuel gauge), tuberous sclerosis complex (TSC), and mammalian 
      target of rapamycin (mTOR). Amino acid deficiencies also up-regulate the 
      expression of p27 using some components of this pathway. (b) 4-Hydroxytamoxifen 
      (but not tamoxifen), genistein (but not genistin), daidzein, and probably other 
      nutritional and chemopreventive anti-cancer agents could up-regulate expression 
      of p27 via receptor protein tyrosine kinases (RPTKs), phosphoinositide 3-kinase 
      (PI3K), phosphoinosite-dependent kinase (PDK), Akt/PKB and mTOR. (c) Expression 
      of p27 could also be up-regulated via RPTKs followed by MAPKs--MEK, ERK and 
      p38MAPK--and probably MNK. Finally, (d) global hypomethylation of 5'-m7G cap of 
      mRNAs could also up-regulate expression of p27. CONCLUSION: Based on these 
      findings, we conclude that various nutritional and chemopreventive anti-cancer 
      agents up-regulate expression of p27 in (pre)neoplastic cells.
FAU - Eto, Isao
AU  - Eto I
AD  - Department of Nutrition Sciences, University of Alabama at Birmingham, 
      Birmingham, Alabama, USA. etoi@uab.edu
LA  - eng
PT  - Journal Article
DEP - 20060809
PL  - England
TA  - Cancer Cell Int
JT  - Cancer cell international
JID - 101139795
PMC - PMC1559648
EDAT- 2006/08/11 09:00
MHDA- 2006/08/11 09:01
PMCR- 2006/08/09
CRDT- 2006/08/11 09:00
PHST- 2006/06/04 00:00 [received]
PHST- 2006/08/09 00:00 [accepted]
PHST- 2006/08/11 09:00 [pubmed]
PHST- 2006/08/11 09:01 [medline]
PHST- 2006/08/11 09:00 [entrez]
PHST- 2006/08/09 00:00 [pmc-release]
AID - 1475-2867-6-20 [pii]
AID - 10.1186/1475-2867-6-20 [doi]
PST - epublish
SO  - Cancer Cell Int. 2006 Aug 9;6:20. doi: 10.1186/1475-2867-6-20.