Publication

RANKL/RANK control Brca1 mutation-driven mammary tumors

Sigl, V., Owusu-Boaitey, K., Joshi, P. A., Kavirayani, A., Wirnsberger, G., Novatchkova, M., Kozieradzki, I., Schramek, D., Edokobi, N., Hersl, J., Sampson, A., Odai-Afotey, A., Lazaro, C., Gonzalez-Suarez, E., Pujana, M. A., Heyn, H., Vidal, E., Cruickshank, J., Berman, H., Sarao, R., Ticevic, M., Uribesalgo, I., Tortola, L., Rao, S., Tan, Y., Pfeiler, G., Lee, E. Y. H. P., Bago-Horvath, Z., Kenner, L., Popper, H., Singer, C., Khokha, R., Jones, L. P., Penninger, J. M. & CIMBA, Jul-2016, In : Cell research. 26, 7, p. 761-774 14 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Sigl, V., Owusu-Boaitey, K., Joshi, P. A., Kavirayani, A., Wirnsberger, G., Novatchkova, M., Kozieradzki, I., Schramek, D., Edokobi, N., Hersl, J., Sampson, A., Odai-Afotey, A., Lazaro, C., Gonzalez-Suarez, E., Pujana, M. A., Heyn, H., Vidal, E., Cruickshank, J., Berman, H., ... CIMBA (2016). RANKL/RANK control Brca1 mutation-driven mammary tumors. Cell research, 26(7), 761-774. https://doi.org/10.1038/cr.2016.69

Author

Sigl, Verena ; Owusu-Boaitey, Kwadwo ; Joshi, Purna A. ; Kavirayani, Anoop ; Wirnsberger, Gerald ; Novatchkova, Maria ; Kozieradzki, Ivona ; Schramek, Daniel ; Edokobi, Nnamdi ; Hersl, Jerome ; Sampson, Aishia ; Odai-Afotey, Ashley ; Lazaro, Conxi ; Gonzalez-Suarez, Eva ; Pujana, Miguel A. ; Heyn, Holger ; Vidal, Enrique ; Cruickshank, Jennifer ; Berman, Hal ; Sarao, Renu ; Ticevic, Melita ; Uribesalgo, Iris ; Tortola, Luigi ; Rao, Shuan ; Tan, Yen ; Pfeiler, Georg ; Lee, Eva Y. H. P. ; Bago-Horvath, Zsuzsanna ; Kenner, Lukas ; Popper, Helmuth ; Singer, Christian ; Khokha, Rama ; Jones, Laundette P. ; Penninger, Josef M. ; CIMBA. / RANKL/RANK control Brca1 mutation-driven mammary tumors. In: Cell research. 2016 ; Vol. 26, No. 7. pp. 761-774.

Harvard

Sigl, V, Owusu-Boaitey, K, Joshi, PA, Kavirayani, A, Wirnsberger, G, Novatchkova, M, Kozieradzki, I, Schramek, D, Edokobi, N, Hersl, J, Sampson, A, Odai-Afotey, A, Lazaro, C, Gonzalez-Suarez, E, Pujana, MA, Heyn, H, Vidal, E, Cruickshank, J, Berman, H, Sarao, R, Ticevic, M, Uribesalgo, I, Tortola, L, Rao, S, Tan, Y, Pfeiler, G, Lee, EYHP, Bago-Horvath, Z, Kenner, L, Popper, H, Singer, C, Khokha, R, Jones, LP, Penninger, JM & CIMBA 2016, 'RANKL/RANK control Brca1 mutation-driven mammary tumors', Cell research, vol. 26, no. 7, pp. 761-774. https://doi.org/10.1038/cr.2016.69

Standard

RANKL/RANK control Brca1 mutation-driven mammary tumors. / Sigl, Verena; Owusu-Boaitey, Kwadwo; Joshi, Purna A.; Kavirayani, Anoop; Wirnsberger, Gerald; Novatchkova, Maria; Kozieradzki, Ivona; Schramek, Daniel; Edokobi, Nnamdi; Hersl, Jerome; Sampson, Aishia; Odai-Afotey, Ashley; Lazaro, Conxi; Gonzalez-Suarez, Eva; Pujana, Miguel A.; Heyn, Holger; Vidal, Enrique; Cruickshank, Jennifer; Berman, Hal; Sarao, Renu; Ticevic, Melita; Uribesalgo, Iris; Tortola, Luigi; Rao, Shuan; Tan, Yen; Pfeiler, Georg; Lee, Eva Y. H. P.; Bago-Horvath, Zsuzsanna; Kenner, Lukas; Popper, Helmuth; Singer, Christian; Khokha, Rama; Jones, Laundette P.; Penninger, Josef M.; CIMBA.

In: Cell research, Vol. 26, No. 7, 07.2016, p. 761-774.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Sigl V, Owusu-Boaitey K, Joshi PA, Kavirayani A, Wirnsberger G, Novatchkova M et al. RANKL/RANK control Brca1 mutation-driven mammary tumors. Cell research. 2016 Jul;26(7):761-774. https://doi.org/10.1038/cr.2016.69


BibTeX

@article{a5d98b019eee4be88def9cbf5f96d3ff,
title = "RANKL/RANK control Brca1 mutation-driven mammary tumors",
abstract = "Breast cancer is the most common female cancer, affecting approximately one in eight women during their lifetime. Besides environmental triggers and hormones, inherited mutations in the breast cancer 1 (BRCA1) or BRCA2 genes markedly increase the risk for the development of breast cancer. Here, using two different mouse models, we show that genetic inactivation of the key osteoclast differentiation factor RANK in the mammary epithelium markedly delayed onset, reduced incidence, and attenuated progression of Brca1; p53 mutation-driven mammary cancer. Long-term pharmacological inhibition of the RANK ligand RANKL in mice abolished the occurrence of Brca1 mutation-driven pre-neoplastic lesions. Mechanistically, genetic inactivation of Rank or RANKL/RANK blockade impaired proliferation and expansion of both murine Brca1; p53 mutant mammary stem cells and mammary progenitors from human BRCA1 mutation carriers. In addition, genome variations within the RANK locus were significantly associated with risk of developing breast cancer in women with BRCA1 mutations. Thus, RANKL/RANK control progenitor cell expansion and tumorigenesis in inherited breast cancer. These results present a viable strategy for the possible prevention of breast cancer in BRCA1 mutant patients.",
keywords = "BRCA1, RANK, RANKL, inherited breast cancer, mammary progenitor cells, SUSCEPTIBILITY GENE BRCA1, NEGATIVE BREAST-CANCER, BONE-MINERAL DENSITY, EPITHELIAL-CELLS, PROGESTERONE-RECEPTOR, POSTMENOPAUSAL WOMEN, PROSTATE-CANCER, MOUSE MAMMARY, MICE, DIFFERENTIATION",
author = "Verena Sigl and Kwadwo Owusu-Boaitey and Joshi, {Purna A.} and Anoop Kavirayani and Gerald Wirnsberger and Maria Novatchkova and Ivona Kozieradzki and Daniel Schramek and Nnamdi Edokobi and Jerome Hersl and Aishia Sampson and Ashley Odai-Afotey and Conxi Lazaro and Eva Gonzalez-Suarez and Pujana, {Miguel A.} and Holger Heyn and Enrique Vidal and Jennifer Cruickshank and Hal Berman and Renu Sarao and Melita Ticevic and Iris Uribesalgo and Luigi Tortola and Shuan Rao and Yen Tan and Georg Pfeiler and Lee, {Eva Y. H. P.} and Zsuzsanna Bago-Horvath and Lukas Kenner and Helmuth Popper and Christian Singer and Rama Khokha and Jones, {Laundette P.} and Penninger, {Josef M.} and CIMBA and Jan Oosterwijk",
year = "2016",
month = jul,
doi = "10.1038/cr.2016.69",
language = "English",
volume = "26",
pages = "761--774",
journal = "Cell research",
issn = "1001-0602",
publisher = "INST BIOCHEMISTRY & CELL BIOLOGY",
number = "7",

}

RIS

TY - JOUR

T1 - RANKL/RANK control Brca1 mutation-driven mammary tumors

AU - Sigl, Verena

AU - Owusu-Boaitey, Kwadwo

AU - Joshi, Purna A.

AU - Kavirayani, Anoop

AU - Wirnsberger, Gerald

AU - Novatchkova, Maria

AU - Kozieradzki, Ivona

AU - Schramek, Daniel

AU - Edokobi, Nnamdi

AU - Hersl, Jerome

AU - Sampson, Aishia

AU - Odai-Afotey, Ashley

AU - Lazaro, Conxi

AU - Gonzalez-Suarez, Eva

AU - Pujana, Miguel A.

AU - Heyn, Holger

AU - Vidal, Enrique

AU - Cruickshank, Jennifer

AU - Berman, Hal

AU - Sarao, Renu

AU - Ticevic, Melita

AU - Uribesalgo, Iris

AU - Tortola, Luigi

AU - Rao, Shuan

AU - Tan, Yen

AU - Pfeiler, Georg

AU - Lee, Eva Y. H. P.

AU - Bago-Horvath, Zsuzsanna

AU - Kenner, Lukas

AU - Popper, Helmuth

AU - Singer, Christian

AU - Khokha, Rama

AU - Jones, Laundette P.

AU - Penninger, Josef M.

AU - CIMBA

AU - Oosterwijk, Jan

PY - 2016/7

Y1 - 2016/7

N2 - Breast cancer is the most common female cancer, affecting approximately one in eight women during their lifetime. Besides environmental triggers and hormones, inherited mutations in the breast cancer 1 (BRCA1) or BRCA2 genes markedly increase the risk for the development of breast cancer. Here, using two different mouse models, we show that genetic inactivation of the key osteoclast differentiation factor RANK in the mammary epithelium markedly delayed onset, reduced incidence, and attenuated progression of Brca1; p53 mutation-driven mammary cancer. Long-term pharmacological inhibition of the RANK ligand RANKL in mice abolished the occurrence of Brca1 mutation-driven pre-neoplastic lesions. Mechanistically, genetic inactivation of Rank or RANKL/RANK blockade impaired proliferation and expansion of both murine Brca1; p53 mutant mammary stem cells and mammary progenitors from human BRCA1 mutation carriers. In addition, genome variations within the RANK locus were significantly associated with risk of developing breast cancer in women with BRCA1 mutations. Thus, RANKL/RANK control progenitor cell expansion and tumorigenesis in inherited breast cancer. These results present a viable strategy for the possible prevention of breast cancer in BRCA1 mutant patients.

AB - Breast cancer is the most common female cancer, affecting approximately one in eight women during their lifetime. Besides environmental triggers and hormones, inherited mutations in the breast cancer 1 (BRCA1) or BRCA2 genes markedly increase the risk for the development of breast cancer. Here, using two different mouse models, we show that genetic inactivation of the key osteoclast differentiation factor RANK in the mammary epithelium markedly delayed onset, reduced incidence, and attenuated progression of Brca1; p53 mutation-driven mammary cancer. Long-term pharmacological inhibition of the RANK ligand RANKL in mice abolished the occurrence of Brca1 mutation-driven pre-neoplastic lesions. Mechanistically, genetic inactivation of Rank or RANKL/RANK blockade impaired proliferation and expansion of both murine Brca1; p53 mutant mammary stem cells and mammary progenitors from human BRCA1 mutation carriers. In addition, genome variations within the RANK locus were significantly associated with risk of developing breast cancer in women with BRCA1 mutations. Thus, RANKL/RANK control progenitor cell expansion and tumorigenesis in inherited breast cancer. These results present a viable strategy for the possible prevention of breast cancer in BRCA1 mutant patients.

KW - BRCA1

KW - RANK

KW - RANKL

KW - inherited breast cancer

KW - mammary progenitor cells

KW - SUSCEPTIBILITY GENE BRCA1

KW - NEGATIVE BREAST-CANCER

KW - BONE-MINERAL DENSITY

KW - EPITHELIAL-CELLS

KW - PROGESTERONE-RECEPTOR

KW - POSTMENOPAUSAL WOMEN

KW - PROSTATE-CANCER

KW - MOUSE MAMMARY

KW - MICE

KW - DIFFERENTIATION

U2 - 10.1038/cr.2016.69

DO - 10.1038/cr.2016.69

M3 - Article

VL - 26

SP - 761

EP - 774

JO - Cell research

JF - Cell research

SN - 1001-0602

IS - 7

ER -

ID: 49401081