PMID- 10066798
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 11
DP  - 1999 Mar 12
TI  - pp60(v-src) induction of cyclin D1 requires collaborative interactions between
      the extracellular signal-regulated kinase, p38, and Jun kinase pathways. A role
      for cAMP response element-binding protein and activating transcription factor-2
      in pp60(v-src) signaling in breast cancer cells.
PG  - 7341-50
AB  - The cyclin D1 gene is overexpressed in breast tumors and encodes a regulatory
      subunit of cyclin-dependent kinases that phosphorylate the retinoblastoma
      protein. pp60(c-src) activity is frequently increased in breast tumors; however, 
      the mechanisms governing pp60(c-src) regulation of the cell cycle in breast
      epithelium are poorly understood. In these studies, pp60(v-src) induced cyclin D1
      protein levels and promoter activity (48-fold) in MCF7 cells. Cyclin
      D1-associated kinase activity and protein levels were increased in mammary tumors
      from murine mammary tumor virus-pp60(c-src527F) transgenic mice. Optimal
      induction of cyclin D1 by pp60(v-src) involved the extracellular signal-regulated
      kinase, p38, and c-Jun N-terminal kinase members of the mitogen-activated protein
      kinase family. Cyclin D1 promoter activation by pp60(v-src) involved a cAMP
      response element-binding protein (CREB)/activating transcription factor 2 (ATF-2)
      binding site. Dominant negative mutants of CREB and ATF-2 but not c-Jun inhibited
      pp60(v-src) induction of cyclin D1. pp60(v-src) induction of CREB was blocked by 
      the p38 inhibitor SB203580 or by mutation of CREB at Ser133. pp60(v-src)
      induction of ATF-2 was abolished by the c-Jun N-terminal kinase inhibitor
      JNK-interacting protein-1 or by mutation of ATF-2 at Thr69 and Thr71. CREB and
      ATF-2, which bind to a common pp60(v-src) response element, are transcriptionally
      activated by distinct mitogen-activated protein kinases. Induction of cyclin D1
      activity by pp60(v-src) may contribute to breast tumorigenesis through
      phosphorylation and inactivation of the retinoblastoma protein.
FAU - Lee, R J
AU  - Lee RJ
AD  - Departments of Developmental and Molecular Biology and Medicine, Albert Einstein 
      Cancer Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
FAU - Albanese, C
AU  - Albanese C
FAU - Stenger, R J
AU  - Stenger RJ
FAU - Watanabe, G
AU  - Watanabe G
FAU - Inghirami, G
AU  - Inghirami G
FAU - Haines, G K 3rd
AU  - Haines GK 3rd
FAU - Webster, M
AU  - Webster M
FAU - Muller, W J
AU  - Muller WJ
FAU - Brugge, J S
AU  - Brugge JS
FAU - Davis, R J
AU  - Davis RJ
FAU - Pestell, R G
AU  - Pestell RG
LA  - eng
GR  - P50-HL56399/HL/NHLBI NIH HHS/United States
GR  - R29CA70897/CA/NCI NIH HHS/United States
GR  - RI1 CA75503/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Activating Transcription Factor 2)
RN  - 0 (Atf2 protein, mouse)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Transcription Factors)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 2.7.10.2 (Oncogene Protein pp60(v-src))
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Activating Transcription Factor 2
MH  - Animals
MH  - Breast Neoplasms/*metabolism/pathology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cyclin D1/*biosynthesis/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Mice
MH  - Mice, Transgenic
MH  - *Mitogen-Activated Protein Kinases
MH  - Oncogene Protein pp60(v-src)/*metabolism
MH  - Plasmids
MH  - Promoter Regions, Genetic
MH  - Protein Binding
MH  - *Signal Transduction
MH  - Transcription Factors/metabolism
MH  - Tumor Cells, Cultured
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/03/06 03:11
MHDA- 2001/03/28 10:01
CRDT- 1999/03/06 03:11
PHST- 1999/03/06 03:11 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/03/06 03:11 [entrez]
AID - 10.1074/jbc.274.11.7341 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 12;274(11):7341-50. doi: 10.1074/jbc.274.11.7341.