Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model

Ralph Meuwissen; Sabine C. Linn; R. Ilona Linnoila; John Zevenhoven; Wolter J. Mooi; Anton Berns

doi:10.1016/S1535-6108(03)00220-4

Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model

Ralph Meuwissen, Sabine C. Linn, R. Ilona Linnoila, John Zevenhoven, Wolter J. Mooi, Anton Berns^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

446 Citations (Scopus)

Abstract

Small cell lung cancer (SCLC) is a highly aggressive human tumor with a more than 95% mortality rate. Its ontogeny and molecular pathogenesis remains poorly understood. We established a mouse model for neuroendocrine (NE) lung tumors by conditional inactivation of Rb1 and Trp53 in mouse lung epithelial cells. Mice carrying conditional alleles for both Rb1 and Trp53 developed with high incidence aggressive lung tumors with striking morphologic and immunophenotypic similarities to SCLC. Most of these tumors, which we designate MSCLC (murine small cell lung carcinoma), diffusely spread through the lung and gave rise to extrapulmonary metastases. In our model, inactivation of both Rb1 and p53 was a prerequisite for the pathogenesis of SCLC.

Original language	English
Pages (from-to)	181-189
Number of pages	9
Journal	Cancer Cell
Volume	4
Issue number	3
DOIs	https://doi.org/10.1016/S1535-6108(03)00220-4
Publication status	Published - 1 Sept 2003
Externally published	Yes

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@article{7b24493b926240b7a3b01569c0f7705d,

title = "Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model",

abstract = "Small cell lung cancer (SCLC) is a highly aggressive human tumor with a more than 95\% mortality rate. Its ontogeny and molecular pathogenesis remains poorly understood. We established a mouse model for neuroendocrine (NE) lung tumors by conditional inactivation of Rb1 and Trp53 in mouse lung epithelial cells. Mice carrying conditional alleles for both Rb1 and Trp53 developed with high incidence aggressive lung tumors with striking morphologic and immunophenotypic similarities to SCLC. Most of these tumors, which we designate MSCLC (murine small cell lung carcinoma), diffusely spread through the lung and gave rise to extrapulmonary metastases. In our model, inactivation of both Rb1 and p53 was a prerequisite for the pathogenesis of SCLC.",

author = "Ralph Meuwissen and Linn, \{Sabine C.\} and Linnoila, \{R. Ilona\} and John Zevenhoven and Mooi, \{Wolter J.\} and Anton Berns",

note = "Funding Information: We thank L. Rijswijk and F. van de Ah{\'e} for expert assistance with the microsurgical procedures, J. Bulthuis, K. de Goeij, M. Tjin-a-Koeng, and Xu Naizhen for histotechnical assistance, N. Bosnie and A. Zwerver for animal care, and F. DeMayo for providing us with anti-CC10 antibody. S.C.L. was a recipient of a Dutch Cancer Society research fellowship. This work was supported by a grant of the Dutch Cancer Society (R.M.).",

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doi = "10.1016/S1535-6108(03)00220-4",

language = "English",

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T1 - Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model

AU - Meuwissen, Ralph

AU - Linn, Sabine C.

AU - Linnoila, R. Ilona

AU - Zevenhoven, John

AU - Mooi, Wolter J.

AU - Berns, Anton

N1 - Funding Information: We thank L. Rijswijk and F. van de Ahé for expert assistance with the microsurgical procedures, J. Bulthuis, K. de Goeij, M. Tjin-a-Koeng, and Xu Naizhen for histotechnical assistance, N. Bosnie and A. Zwerver for animal care, and F. DeMayo for providing us with anti-CC10 antibody. S.C.L. was a recipient of a Dutch Cancer Society research fellowship. This work was supported by a grant of the Dutch Cancer Society (R.M.).

PY - 2003/9/1

Y1 - 2003/9/1

N2 - Small cell lung cancer (SCLC) is a highly aggressive human tumor with a more than 95% mortality rate. Its ontogeny and molecular pathogenesis remains poorly understood. We established a mouse model for neuroendocrine (NE) lung tumors by conditional inactivation of Rb1 and Trp53 in mouse lung epithelial cells. Mice carrying conditional alleles for both Rb1 and Trp53 developed with high incidence aggressive lung tumors with striking morphologic and immunophenotypic similarities to SCLC. Most of these tumors, which we designate MSCLC (murine small cell lung carcinoma), diffusely spread through the lung and gave rise to extrapulmonary metastases. In our model, inactivation of both Rb1 and p53 was a prerequisite for the pathogenesis of SCLC.

AB - Small cell lung cancer (SCLC) is a highly aggressive human tumor with a more than 95% mortality rate. Its ontogeny and molecular pathogenesis remains poorly understood. We established a mouse model for neuroendocrine (NE) lung tumors by conditional inactivation of Rb1 and Trp53 in mouse lung epithelial cells. Mice carrying conditional alleles for both Rb1 and Trp53 developed with high incidence aggressive lung tumors with striking morphologic and immunophenotypic similarities to SCLC. Most of these tumors, which we designate MSCLC (murine small cell lung carcinoma), diffusely spread through the lung and gave rise to extrapulmonary metastases. In our model, inactivation of both Rb1 and p53 was a prerequisite for the pathogenesis of SCLC.

UR - https://www.scopus.com/pages/publications/0141523025

U2 - 10.1016/S1535-6108(03)00220-4

DO - 10.1016/S1535-6108(03)00220-4

M3 - Article

C2 - 14522252

AN - SCOPUS:0141523025

SN - 1535-6108

VL - 4

SP - 181

EP - 189

JO - Cancer Cell

JF - Cancer Cell

IS - 3

ER -

Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model

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