Ectopic expression of cyclin E in estrogen responsive cells abrogates antiestrogen mediated growth arrest

Navdeep K. Dhillon, Maria Mudryj

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Estrogens stimulate proliferation of estrogen receptor positive MCF7 breast cancer cells while ant/estrogens signal a G0/G1 growth arrest. In MCF7 cells, arrest is mediated through the CDK inhibitors p21 and p27 and through a decrease in cyclin E/CDK2 kinase activity. We found that in MCF7 cells, overexpression of cyclin E partially abrogates a tamoxifen mediated growth arrest. Overexpression of cyclin E is accompanied by a decrease in the levels of RB and CDK inhibitor p21 but an increase in CDK inhibitor p27. Cyclin E overexpression also alters the composition of E2F transcription factor complexes. The E2F4/p107/cyclin E/CDK2 complex, a minor component in proliferating control cells that is absent in growth-arrested cells, is more abundant in both proliferating and tamoxifen treated cyclin E overexpressing cells. Conversely, levels of the quiescence associated E2F/p130 complex is not detected in these cells. Expression from the E2F dependant promoter is elevated in proliferating and tamoxifen treated cyclin E over-expressing cells. This study suggests that a modest overexpression of cyclin E abrogates the tamoxifen mediated growth arrest through modification of the RB/E2F pathway. Moreover, these results provide one explanation of why some cells that express the estrogen receptor may be unresponsive to antiestrogens.

Original languageEnglish (US)
Pages (from-to)4626-4634
Number of pages9
JournalOncogene
Volume21
Issue number30
DOIs
StatePublished - Jul 11 2002

Fingerprint

Cyclin E
Estrogen Receptor Modulators
Estrogens
Tamoxifen
Growth
Cyclin-Dependent Kinase Inhibitor p27
MCF-7 Cells
Estrogen Receptors
E2F Transcription Factors
Ants
Ectopic Gene Expression
Phosphotransferases
Breast Neoplasms

Keywords

  • Breast cancer
  • Cell cycle
  • Cyclin E
  • MCF7
  • Tamoxifen

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Ectopic expression of cyclin E in estrogen responsive cells abrogates antiestrogen mediated growth arrest. / Dhillon, Navdeep K.; Mudryj, Maria.

In: Oncogene, Vol. 21, No. 30, 11.07.2002, p. 4626-4634.

Research output: Contribution to journalArticle

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