PMID- 10435640
OWN - NLM
STAT- MEDLINE
DCOM- 19990819
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 29
DP  - 1999 Jul 22
TI  - Tamoxifen induces p21WAF1 and p27KIP1 expression in estrogen receptor-negative 
      lung cancer cells.
PG  - 4269-74
AB  - Tamoxifen (Tam), besides its action as an anti-estrogen, also inhibits cell 
      proliferation of estrogen receptor (ER)-negative cancer cells by an unknown 
      mechanism. In this study, we used ER-negative lung cancer cells to clarify such 
      ER-independent inhibitory effect of Tam. We found that Tam induced G1 growth 
      arrest in these cells. However, our results indicated that the expression of G1 
      cyclins (including D1, 2, 3 and E) was not regulated by Tam in these lung cancer 
      cells. Additionally, the protein levels of G1 acting cyclin-dependent kinases 
      (CDKs), CDK2, 4 and 6, was unaltered in Tam-treated lung cancer cells with the 
      exception of CDK2 expression in H322 cells which was attenuated by Tam in a cell 
      line-specific manner. We next examined the effect of Tam on the expression of 
      cyclin-dependent kinase inhibitors (CDKIs) and our results demonstrated that the 
      expression of p21WAF1 and p27KIP1, but not p57KIP2, was strongly activated by Tam 
      in these cells. The amounts of p21WAF1 and p27KIP1 co-immunoprecipitated with 
      cyclin E were obviously increased after Tam treatment and reduced activity of 
      cyclin E-associated kinases and accumulation of hypo-phosphorylated 
      retinoblastoma (Rb) protein were clearly detected in Tam-incubated cells. No 
      consentaneous induction of CDKIs was found when ER-negative lung cancer cells 
      were incubated with cytotoxic drugs, cisplatin and etoposide, this indicates that 
      enhancement of CDKI expression is not a non-specific effect of Tam. We also found 
      that Tam may up-regulate p21WAF1 expression via transcription activation. 
      Considered together, these results suggest that Tam-induced growth inhibition in 
      ER-negative lung cancer cells is associated with induction of p21WAF1 and 
      p27KIP1.
FAU - Lee, T H
AU  - Lee TH
AD  - Graduate Institute of Medicine, Kaohsiung Medical College, Taiwan, Republic of 
      China.
FAU - Chuang, L Y
AU  - Chuang LY
FAU - Hung, W C
AU  - Hung WC
LA  - eng
PT  - Journal Article
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
SB  - IM
MH  - Antineoplastic Agents, Hormonal/*pharmacology
MH  - Carcinoma, Non-Small-Cell Lung/genetics/*pathology
MH  - *Cell Cycle Proteins
MH  - Cell Division/drug effects
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclin-Dependent Kinase Inhibitor p27
MH  - Cyclins/*biosynthesis/genetics
MH  - G1 Phase/drug effects
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Lung Neoplasms/genetics/*pathology
MH  - Microtubule-Associated Proteins/*biosynthesis/genetics
MH  - Neoplasm Proteins/analysis/*biosynthesis/genetics
MH  - Receptors, Estrogen/*analysis
MH  - Retinoblastoma Protein/metabolism
MH  - Stimulation, Chemical
MH  - Tamoxifen/*pharmacology
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured/drug effects/metabolism
MH  - *Tumor Suppressor Proteins
EDAT- 1999/08/06 00:00
MHDA- 1999/08/06 00:01
CRDT- 1999/08/06 00:00
PHST- 1999/08/06 00:00 [pubmed]
PHST- 1999/08/06 00:01 [medline]
PHST- 1999/08/06 00:00 [entrez]
AID - 10.1038/sj.onc.1202755 [doi]
PST - ppublish
SO  - Oncogene. 1999 Jul 22;18(29):4269-74. doi: 10.1038/sj.onc.1202755.