Expression of cyclins E1 and E2 during mouse development and in neoplasia

Yan Geng, Qunyan Yu, Wendy Whoriskey, Fred Dick, Kenneth Y. Tsai, Heide L. Ford, Debajit K. Biswas, Arthur B. Pardee, Bruno Amati, Tyler Jacks, Andrea Richardson, Nicholas Dyson, Piotr Sicinski

Research output: Contribution to journalArticle

Abstract

Cyclin E1 (formerly called cyclin E) and the recently described cyclin E2 belong to the family of E-type cyclins that operate during the G1/S phase progression in mammalian cells. The two E-cyclins share a catalytic partner, cyclin-dependent kinase 2 (CDK2), and activate their associated kinase activities at similar times during cell cycle progression. Despite these similarities, it is unknown whether the two proteins perform distinct functions, or, alternatively, they control S-phase entry of different cell types in a tissue-specific fashion. To start addressing in vivo functions of E-cyclins, we determined the expression pattern of cyclins E1 and E2 during normal mouse development. We found that the two E-cyclins showed very similar patterns of expression; both were expressed within the proliferating compartment during embryo development. Analyses of cells and tissues lacking members of the retinoblastoma (pRB) family of proteins revealed that the expression of both cyclins is controlled in a pRB-dependent, but p107- and p130-independent fashion, likely through the pRB-dependent E2F transcription factors. We also found that cyclins E1 and E2 are expressed at high levels in mouse breast tumors driven by the Myc oncogene. Last, we found that cyclin E2 is overexpressed in ≈24% of analyzed human mammary carcinomas. Collectively these findings suggest that the expression of cyclins E1 and E2 is governed by similar molecular circuitry.

Original languageEnglish
Pages (from-to)13138-13143
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number23
DOIs
Publication statusPublished - Nov 6 2001

ASJC Scopus subject areas

  • Genetics
  • General

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    Geng, Y., Yu, Q., Whoriskey, W., Dick, F., Tsai, K. Y., Ford, H. L., Biswas, D. K., Pardee, A. B., Amati, B., Jacks, T., Richardson, A., Dyson, N., & Sicinski, P. (2001). Expression of cyclins E1 and E2 during mouse development and in neoplasia. Proceedings of the National Academy of Sciences of the United States of America, 98(23), 13138-13143. https://doi.org/10.1073/pnas.231487798