PMID- 12671535
OWN - NLM
STAT- MEDLINE
DCOM- 20030915
LR  - 20191025
IS  - 0959-8278 (Print)
IS  - 0959-8278 (Linking)
VI  - 12
IP  - 2
DP  - 2003 Apr
TI  - Multiple effects of alpha1-antitrypsin on breast carcinoma MDA-MB 468 cell growth 
      and invasiveness.
PG  - 117-24
AB  - The degradation of extracellular matrix during cancer invasion results from the 
      action of several protease and protease inhibitor systems. Alpha(1)-Antitrypsin 
      (AAT) is a serine proteinase inhibitor produced by various tumour cells, and its 
      plasma concentration rises during inflammation, infection and malignant diseases. 
      AAT is found in a native, inhibitory active form, but also in other, 
      non-inhibitory forms including cleaved and/or degraded. To test a hypothesis that 
      AAT dependent on its molecular form may have multiple effects on tumour cell 
      behaviour, breast cancer cells, MDA-MB 468, were cultured alone or stimulated 
      with a native AAT or its C-terminal fragment (C-36) at a concentration of 5 
      micromol/l for 2, 24 and 48 hours. Native AAT added to the cells for 2 hours 
      enhanced transforming growth factor beta 1 (TGFbeta1) levels by 50%, but 
      inhibited cell proliferation (by 61%), reduced interleukin 6 (IL-6) levels (by 
      87%) and activity (by about 66%), compared with non-stimulated cells. Native AAT 
      showed similar, but less pronounced, effects when added to the cells for 24 and 
      48 hours. Under the same experimental conditions the cells exposed to the C-36 
      peptide significantly increased in proliferation, invasiveness and showed higher 
      IL-6 levels. In addition, cells treated with the C-36 for 48 hours increased in 
      NFkappaB (nuclear factor kappa B) activity. These results indicate that AAT, 
      dependent on its molecular form, can both suppress and induce breast tumour cell 
      biological activity in vitro.
FAU - Zelvyte, I
AU  - Zelvyte I
AD  - Department of Medicine, University Hospital Malmo, Malmo, Sweden.
FAU - Lindgren, S
AU  - Lindgren S
FAU - Janciauskiene, S
AU  - Janciauskiene S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Cancer Prev
JT  - European journal of cancer prevention : the official journal of the European 
      Cancer Prevention Organisation (ECP)
JID - 9300837
RN  - 0 (Interleukin-6)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (alpha 1-Antitrypsin)
SB  - IM
MH  - Breast Neoplasms/*metabolism/pathology
MH  - Cell Division/*drug effects
MH  - Female
MH  - Humans
MH  - Interleukin-6/metabolism
MH  - Neoplasm Invasiveness/pathology
MH  - Transforming Growth Factor beta/metabolism
MH  - Transforming Growth Factor beta1
MH  - Tumor Cells, Cultured/drug effects
MH  - alpha 1-Antitrypsin/*pharmacology
EDAT- 2003/04/03 05:00
MHDA- 2003/09/16 05:00
CRDT- 2003/04/03 05:00
PHST- 2003/04/03 05:00 [pubmed]
PHST- 2003/09/16 05:00 [medline]
PHST- 2003/04/03 05:00 [entrez]
AID - 10.1097/00008469-200304000-00005 [doi]
PST - ppublish
SO  - Eur J Cancer Prev. 2003 Apr;12(2):117-24. doi: 10.1097/00008469-200304000-00005.