Skip to main content
Top
Published in: Breast Cancer Research 4/2002

01-08-2002 | Commentary

Cyclins in breast cancer: too much of a good thing

Author: Greg H Enders

Published in: Breast Cancer Research | Issue 4/2002

Login to get access

Abstract

Cyclin E, a key mediator of entry into the cell division cycle, is expressed abundantly in many breast cancers. However, amplification of the cognate gene is observed rarely, leaving the responsible mechanism(s) and its importance in tumorigenesis in doubt. In a recent report, Steve Reed's lab demonstrates that hCdc4/Fbw7 targets cyclin E for ubiquitin-mediated proteolysis and is mutant in a breast cancer cell line with high cyclin E levels. Independent work demonstrates that a Drosophila hCdc4 homologue constrains cyclin E expression in vivo. These results suggest that lesions in protein degradation pathways may contribute to cyclin E deregulation in breast cancer.
Literature
1.
2.
3.
go back to reference Strohmaier H, Spruck CH, Kaiser P, Won KA, Sangfelt O, Reed SI: Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature. 2001, 413: 316-322. 10.1038/35095076.CrossRefPubMed Strohmaier H, Spruck CH, Kaiser P, Won KA, Sangfelt O, Reed SI: Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature. 2001, 413: 316-322. 10.1038/35095076.CrossRefPubMed
4.
go back to reference Courjal F, Louason G, Speiser P, Katsaros D, Zeillinger R, Theillet C: Cyclin gene amplification and overexpression in breast and ovarian cancers: evidence for the selection of cyclin D1 in breast and cyclin E in ovarian tumors. Int J Cancer. 1996, 69: 247-253. 10.1002/(SICI)1097-0215(19960822)69:4<247::AID-IJC1>3.3.CO;2-Q.CrossRefPubMed Courjal F, Louason G, Speiser P, Katsaros D, Zeillinger R, Theillet C: Cyclin gene amplification and overexpression in breast and ovarian cancers: evidence for the selection of cyclin D1 in breast and cyclin E in ovarian tumors. Int J Cancer. 1996, 69: 247-253. 10.1002/(SICI)1097-0215(19960822)69:4<247::AID-IJC1>3.3.CO;2-Q.CrossRefPubMed
5.
go back to reference Wang TC, Cardiff RD, Zukerberg L, Lees E, Arnold A, Schmidt EV: Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature. 1994, 369: 669-671. 10.1038/369669a0.CrossRefPubMed Wang TC, Cardiff RD, Zukerberg L, Lees E, Arnold A, Schmidt EV: Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice. Nature. 1994, 369: 669-671. 10.1038/369669a0.CrossRefPubMed
6.
go back to reference Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Hasla SZ, Bronson RT, Elledge S, Weinberg RA: Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell. 1995, 82: 621-630.CrossRefPubMed Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Hasla SZ, Bronson RT, Elledge S, Weinberg RA: Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell. 1995, 82: 621-630.CrossRefPubMed
7.
go back to reference Fantl V, Stamp G, Andrews A, Rosewell I, Dickson C: Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. Genes Dev. 1995, 9: 2364-2372.CrossRefPubMed Fantl V, Stamp G, Andrews A, Rosewell I, Dickson C: Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. Genes Dev. 1995, 9: 2364-2372.CrossRefPubMed
8.
go back to reference Yu Q, Geng Y, Sicinski P: Specific protection against breast cancers by cyclin D1 ablation. Nature. 2001, 411: 1017-1021. 10.1038/35082500.CrossRefPubMed Yu Q, Geng Y, Sicinski P: Specific protection against breast cancers by cyclin D1 ablation. Nature. 2001, 411: 1017-1021. 10.1038/35082500.CrossRefPubMed
9.
go back to reference Spruck CH, Won KA, Reed SI: Deregulated cyclin E induces chromosome instability. Nature. 1999, 401: 297-300. 10.1038/45836.CrossRefPubMed Spruck CH, Won KA, Reed SI: Deregulated cyclin E induces chromosome instability. Nature. 1999, 401: 297-300. 10.1038/45836.CrossRefPubMed
10.
go back to reference Bortne DM, Rosenberg MP: Induction of mammary gland hyperplasia and carcinomas in transgenic mice expressing human cyclin E. Mol Cell Biol. 1997, 17: 453-459.CrossRef Bortne DM, Rosenberg MP: Induction of mammary gland hyperplasia and carcinomas in transgenic mice expressing human cyclin E. Mol Cell Biol. 1997, 17: 453-459.CrossRef
11.
go back to reference Dutta A, Chandra R, Leiter LM, Lester S: Cyclins as markers of tumor proliferation: immunocytochemical studies in breast cancer. Proc Natl Acad Sci USA. 1995, 92: 5386-5390.CrossRefPubMedPubMedCentral Dutta A, Chandra R, Leiter LM, Lester S: Cyclins as markers of tumor proliferation: immunocytochemical studies in breast cancer. Proc Natl Acad Sci USA. 1995, 92: 5386-5390.CrossRefPubMedPubMedCentral
12.
go back to reference Porter PL, Malone KE, Heagerty PJ, Alexander GM, Gatti LA, Firpo EJ, Daling JR, Roberts JM: Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients. Nat Med. 1997, 3: 222-225.CrossRefPubMed Porter PL, Malone KE, Heagerty PJ, Alexander GM, Gatti LA, Firpo EJ, Daling JR, Roberts JM: Expression of cell-cycle regulators p27Kip1 and cyclin E, alone and in combination, correlate with survival in young breast cancer patients. Nat Med. 1997, 3: 222-225.CrossRefPubMed
13.
go back to reference Won KA, Reed SI: Activation of cyclin E/CDK2 is coupled to site-specific autophosphorylation and ubiquitin-dependent degradation of cyclin E. EMBO J. 1996, 15: 4182-4193.PubMedPubMedCentral Won KA, Reed SI: Activation of cyclin E/CDK2 is coupled to site-specific autophosphorylation and ubiquitin-dependent degradation of cyclin E. EMBO J. 1996, 15: 4182-4193.PubMedPubMedCentral
14.
go back to reference Clurman BE, Sheaff RJ, Thress K, Groudine M, Roberts JM: Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation. Genes Dev. 1996, 10: 1979-1990.CrossRefPubMed Clurman BE, Sheaff RJ, Thress K, Groudine M, Roberts JM: Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation. Genes Dev. 1996, 10: 1979-1990.CrossRefPubMed
15.
go back to reference Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ: SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell. 1996, 86: 263-274.CrossRefPubMed Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ: SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell. 1996, 86: 263-274.CrossRefPubMed
16.
go back to reference DeSalle LM, Pagano M: Regulation of the G1 to S transition by the ubiquitin pathway. FEBS Lett. 2001, 490: 179-189. 10.1016/S0014-5793(01)02121-4.CrossRefPubMed DeSalle LM, Pagano M: Regulation of the G1 to S transition by the ubiquitin pathway. FEBS Lett. 2001, 490: 179-189. 10.1016/S0014-5793(01)02121-4.CrossRefPubMed
17.
go back to reference Tyers M, Jorgensen P: Proteolysis and the cell cycle: with this RING I do thee destroy. Curr Opin Genet Dev. 2000, 10: 54-64. 10.1016/S0959-437X(99)00049-0.CrossRefPubMed Tyers M, Jorgensen P: Proteolysis and the cell cycle: with this RING I do thee destroy. Curr Opin Genet Dev. 2000, 10: 54-64. 10.1016/S0959-437X(99)00049-0.CrossRefPubMed
18.
go back to reference Nash P, Tang X, Orlicky S, Chen Q, Gertler FB, Mendenhall MD, Sicheri F, Pawson T, Tyers M: Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication. Nature. 2001, 414: 514-521. 10.1016/S0014-5793(97)01059-4.CrossRefPubMed Nash P, Tang X, Orlicky S, Chen Q, Gertler FB, Mendenhall MD, Sicheri F, Pawson T, Tyers M: Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication. Nature. 2001, 414: 514-521. 10.1016/S0014-5793(97)01059-4.CrossRefPubMed
19.
go back to reference Koepp DM, Schaefer LK, Ye X, Keyomarsi K, Chu C, Harper JW, Elledge SJ: Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science. 2001, 294: 173-177. 10.1126/science.1065203.CrossRefPubMed Koepp DM, Schaefer LK, Ye X, Keyomarsi K, Chu C, Harper JW, Elledge SJ: Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science. 2001, 294: 173-177. 10.1126/science.1065203.CrossRefPubMed
20.
go back to reference Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW: A family of mammalian F-box proteins. Curr Biol. 1999, 9: 1180-1182. 10.1016/S0960-9822(00)80021-4.CrossRefPubMed Winston JT, Koepp DM, Zhu C, Elledge SJ, Harper JW: A family of mammalian F-box proteins. Curr Biol. 1999, 9: 1180-1182. 10.1016/S0960-9822(00)80021-4.CrossRefPubMed
21.
go back to reference Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M: Identification of a family of human F-box proteins. Curr Biol. 1999, 9: 1177-1179. 10.1016/S0960-9822(00)80020-2.CrossRefPubMed Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M: Identification of a family of human F-box proteins. Curr Biol. 1999, 9: 1177-1179. 10.1016/S0960-9822(00)80020-2.CrossRefPubMed
22.
go back to reference Moberg KH, Bell DW, Wahrer DC, Haber DA, Harihara IK: Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines. Nature. 2001, 413: 311-316. 10.1016/S0370-2693(97)01128-3.CrossRefPubMed Moberg KH, Bell DW, Wahrer DC, Haber DA, Harihara IK: Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines. Nature. 2001, 413: 311-316. 10.1016/S0370-2693(97)01128-3.CrossRefPubMed
23.
go back to reference Schutte M, Hruba RH, Geradts J, Maynard R, Hilgers W, Rabindra SK, Moskaluk CA, Hahn SA, Schwarte-Waldhoff I, Schmiegel W, Bayli SB, Ker SE, Herman JG: Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res. 1997, 57: 3126-3130.PubMed Schutte M, Hruba RH, Geradts J, Maynard R, Hilgers W, Rabindra SK, Moskaluk CA, Hahn SA, Schwarte-Waldhoff I, Schmiegel W, Bayli SB, Ker SE, Herman JG: Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res. 1997, 57: 3126-3130.PubMed
24.
go back to reference Hu B, Mitra J, van den Heuvel S, Enders GH: S and G2 phase roles for Cdk2 revealed by inducible expression of a dominant negative mutant in human cells. Mol Cell Biol. 2001, 21: 2755-2766. 10.1128/MCB.21.8.2755-2766.2001.CrossRefPubMedPubMedCentral Hu B, Mitra J, van den Heuvel S, Enders GH: S and G2 phase roles for Cdk2 revealed by inducible expression of a dominant negative mutant in human cells. Mol Cell Biol. 2001, 21: 2755-2766. 10.1128/MCB.21.8.2755-2766.2001.CrossRefPubMedPubMedCentral
25.
go back to reference Garrett MD, Fattaey A: CDK inhibition and cancer therapy. Curr Opin Genet Dev. 1999, 9: 104-111. 10.1016/S0959-437X(99)80015-X.CrossRefPubMed Garrett MD, Fattaey A: CDK inhibition and cancer therapy. Curr Opin Genet Dev. 1999, 9: 104-111. 10.1016/S0959-437X(99)80015-X.CrossRefPubMed
Metadata
Title
Cyclins in breast cancer: too much of a good thing
Author
Greg H Enders
Publication date
01-08-2002
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 4/2002
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr439

Other articles of this Issue 4/2002

Breast Cancer Research 4/2002 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine