PMID- 10597272
OWN - NLM
STAT- MEDLINE
DCOM- 20000106
LR  - 20061115
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 48
DP  - 1999 Nov 18
TI  - Growth factor-regulated expression of enzymes involved in nucleotide
      biosynthesis: a novel mechanism of growth factor action.
PG  - 6667-76
AB  - Keratinocyte growth factor (KGF) is a potent and specific mitogen for epithelial 
      cells, including the keratinocytes of the skin. We investigated the mechanisms of
      action of KGF by searching for genes which are regulated by this growth factor in
      cultured human keratinocytes. Using the differential display RT-PCR technology we
      identified the gene encoding adenylosuccinate lyase [EC 4.3.2.2] as a novel
      KGF-regulated gene. Adenylosuccinate lyase plays an important role in purine de
      novo synthesis. To gain further insight into the potential role of nucleotide
      biosynthesis in the mitogenic effect of KGF, we cloned cDNA fragments of the key 
      regulatory enzymes involved in purine and pyrimidine metabolism (adenylosuccinate
      synthetase [EC 6.3.4.4], phosphoribosyl pyrophosphate synthetase [EC 2.7.6.1],
      amidophosphoribosyl transferase [EC 2.4.2.14], hypoxanthine guanine
      phosphoribosyl transferase [EC 2.4.2.8] and the multifunctional protein CAD which
      includes the enzymatic activities of carbamoyl-phosphate synthetase II [EC
      6.3.5.59], aspartate transcarbamylase [EC 2.1.3.2] and dihydroorotase [EC
      3.5.2.3]). Expression of all of these enzymes was upregulated after treatment
      with KGF and also with epidermal growth factor (EGF), indicating that these
      mitogens stimulate nucleotide production by induction of these enzymes. To
      determine a possible in vivo correlation between the expression of KGF, EGF and
      the enzymes mentioned above, we analysed the expression of the enzymes during
      cutaneous wound repair, where high levels of these mitogens are present. Indeed, 
      we found a strong mRNA expression of all of these enzymes in the EGF- and
      KGF-responsive keratinocytes of the hyperproliferative epithelium at the wound
      edge, indicating that their expression might also be regulated by growth factors 
      during wound healing.
FAU - Gassmann, M G
AU  - Gassmann MG
AD  - Max-Planck-Institute of Biochemistry, Martinsried, Germany.
FAU - Stanzel, A
AU  - Stanzel A
FAU - Werner, S
AU  - Werner S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (DNA Primers)
RN  - 0 (FGF7 protein, human)
RN  - 0 (Fgf7 protein, mouse)
RN  - 0 (Fibroblast Growth Factor 10)
RN  - 0 (Growth Substances)
RN  - 0 (Purine Nucleotides)
RN  - 0 (Pyrimidine Nucleotides)
RN  - 0 (RNA, Messenger)
RN  - 126469-10-1 (Fibroblast Growth Factor 7)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cloning, Molecular
MH  - DNA Primers
MH  - Epidermal Growth Factor/*physiology
MH  - Fibroblast Growth Factor 10
MH  - Fibroblast Growth Factor 7
MH  - *Fibroblast Growth Factors
MH  - Gene Expression Regulation, Enzymologic/*physiology
MH  - Growth Substances/*physiology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Purine Nucleotides/*biosynthesis
MH  - Pyrimidine Nucleotides/*biosynthesis
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Skin/enzymology/injuries
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1038/sj.onc.1203120 [doi]
PST - ppublish
SO  - Oncogene. 1999 Nov 18;18(48):6667-76. doi: 10.1038/sj.onc.1203120.