Research interest
Conditional mouse models of breast cancer
The focus of our laboratory is on the genetic dissection of human breast cancer through the use of advanced mouse models. We have employed Cre/loxP technology to generate mouse strains with conditional mutations in Brca1, Brca2, E-cadherin or p53. We have bred combinations of these mice together with epithelial- or mammary-specific Cre transgenics to produce compound mutant mice that develop mammary tumors with high incidence.
Thus far, models have been developed for p53-induced breast cancer, BRCA1- and BRCA2- associated hereditary breast cancer, and E-cadherin-associated metastatic breast cancer. These models are used to (i) investigate genotype-phenotype relations in mammary tumorigenesis; (ii) identify genetic changes underlying breast carcinogenesis; (iii) study the role of inate and adaptive immunity in breast cancer development; (iv) perform therapeutic intervention and chemoprevention studies.
For these studies we combine in vivo mouse models and in vitro systems (tumor cell lines and primary mammary epithelial cells) with genomics approaches (gene expression profiling, array-CGH) and functional genomics screens (expression cloning, RNAi, transposon tagging).
Key publications
Derksen PW, Liu X, Saridin F, van der Gulden H, Zevenhoven J, Evers B, van Beijnum JR, Griffioen AW, Vink J, Krimpenfort P, Peterse JL, Cardiff RD, Berns A and Jonkers J. (2006). Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis. Cancer Cell 10, 437-449.
Evers B and Jonkers J. (2006). Mouse models of BRCA1 and BRCA2 deficiency: past lessons, current understanding and future prospects. Oncogene 25, 5885-5897.
van Meeteren LA, Ruurs P, Stortelers C, Bouwman P, van Rooijen MA, Pradere JP, Pettit TR, Wakelam MJ, Saulnier-Blache JS, Mummery CL, Moolenaar WH and Jonkers J. (2006). Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol. Cell. Biol. 26, 5015-5022.
Jonkers J and Berns A. (2004). Oncogene addiction: sometimes a temporary slavery. Cancer Cell 6, 535-538.
Chung YJ*, Jonkers J*, Kitson H, Fiegler H, Humphray S, Scott C, Hunt S, Yu Y, Nishijima I, Velds A, Holstege H, Carter NP and Bradley A. (2004). A whole-genome mouse BAC microarray with 1-Mb resolution for analysis of DNA copy number changes by array comparative genomic hybridization. Genome Res. 14, 188-196.
Vooijs M, Jonkers J, Lyons S and Berns A. (2002). Non-invasive imaging of spontaneous retinoblastoma pathway-dependent tumors in mice. Cancer Res. 62, 1862-1867.
Jonkers J and Berns A. (2002). Conditional mouse models of sporadic cancer. Nat. Rev. Cancer 2, 251-265.
Jonkers J, Meuwissen R, van der Gulden H, Peterse H, van der Valk M and Berns A. (2001). Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat. Genet. 29, 418-425.
Loonstra A, Vooijs M, Beverloo B, Al Allak B, van Drunen E, Kanaar R, Berns A and Jonkers J. (2001). Growth inhibition and DNA damage induced by Cre recombinase in mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 98, 9209-9214.
Vooijs M, Jonkers J and Berns A. (2001). A highly efficient ligand-inducible Cre recombinase mouse line shows that loxP recombination is position dependent. EMBO Rep. 2, 292-297.
More publications by Jos Jonkers on PubMed
Biographic sketch
Jos Jonkers performed his PhD research (Thesis: Identification and characterization of the Frat1 proto-oncogene, University of Amsterdam) in the laboratory of Dr Anton Berns at the Netherlands Cancer Institute. During this period he developed an active interest in the utility of retroviral insertional mutagenesis to induce tumors and identify new oncogenes.
In 1996 he became a postdoctoral fellow in the Berns lab. He participated in a large-scale project to generate a comprehensive set of conditional tumor-suppressor knockout mice in combination with a series of (inducible) Cre transgenic mouse lines.
The focus of his research became conditional mouse models for breast cancer. To this end, he has generated Brca1, Brca2, and p53 conditional knockouts, and used (combinations of) these mice together with an epithelial Cre transgenic line to generate compound mutant mice that develop mammary tumors with high incidence.
In 2002, he spent six months as a senior research associate in the laboratory of Dr Allan Bradley at the Wellcome Trust Sanger Institute (Hinxton, UK), where he was involved in setting up mouse CGH using BAC microarrays. In the same year, he was appointed assistant professor at the Netherlands Cancer Institute where he continues his studies on modeling sporadic and hereditary breast cancer in mice.
Co-workers
Boon, Ute Technical staff
Bouwman, Peter PhD Postdoctoral fellow
Braumuller, Tanya Technical staff
Doumont, Gilles PhD Postdoctoral fellow
Drost, Rinske MSc Graduate student
Jaspers, Janneke MSc Graduate student
Klarenbeek, Sjoerd MSc Graduate student
Klijn, Christiaan MSc Graduate student
Michalek, Ewa PhD Postdoctoral fellow
Pieterse, Mark Technical staff
Schut-Kregel, Eva Technical staff
Ter Brugge, Petra PhD Postdoctoral fellow
Van de Ven, Marieke PhD Postdoctoral fellow
Van der Burg, Eline Technical staff
Van der Gulden, Hanneke Technical staff
Van der Heijden, Ingrid Technical staff
Van Miltenburg, Martine PhD Postdoctoral fellow
Wientjens, Ellen Technical staff
De Visser-lab:
De Visser, Karin PhD Research Associate
Ciampricotti, Metamia MSc Graduate student
Doornebal, Chris MSc Graduate student
Hau, Tisee Technical staff
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