Targeted deletion of Wwox reveals a tumor suppressor function

Rami I. Aqeilan; Francesco Trapasso; Sadiq Hussain; Stefan Costinean; Dean Marshall; Yuri Pekarsky; John P. Hagan; Nicola Zanesi; Mohamed Kaou; Gary S. Stein; Jane B. Lian; Carlo M. Croce

doi:10.1073/pnas.0609783104

Targeted deletion of Wwox reveals a tumor suppressor function

Rami I. Aqeilan^*
, Francesco Trapasso
, Sadiq Hussain
, Stefan Costinean
, Dean Marshall
, Yuri Pekarsky
, John P. Hagan
, Nicola Zanesi
, Mohamed Kaou
, Gary S. Stein
, Jane B. Lian
, Carlo M. Croce

^*Corresponding author for this work

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

190 Scopus citations

Abstract

The WW domain-containing oxidoreductase (WWOX) spans the second most common fragile site of the human genome, FRA16D, located at 16q23, and its expression is altered in several types of human cancer. We have previously shown that restoration of WWOX expression in cancer cells suppresses tumorigenicity. To investigate WWOX tumor suppressor function in vivo, we generated mice carrying a targeted deletion of the Wwox gene and monitored incidence of tumor formation. Osteosarcomas in juvenile Wwox^-/- and lung papillary carcinoma in adult Wwox^+/- mice occurred spontaneously. In addition, Wwox ^+/- mice develop significantly more ethyl nitrosourea-induced lung tumors and lymphomas in comparison to wild-type littermate mice. Intriguingly, these tumors still express Wwox protein, suggesting haploinsuffiency of WWOX itself is cancer predisposing. These results indicate that WWOX is a bona fide tumor suppressor.

Original language	English
Pages (from-to)	3949-3954
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	104
Issue number	10
DOIs	https://doi.org/10.1073/pnas.0609783104
State	Published - 6 Mar 2007
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Common fragile site
FHIT
Knockout
Lung cancer
Osteosarcoma

Access to Document

10.1073/pnas.0609783104

Cite this

Aqeilan, R. I., Trapasso, F., Hussain, S., Costinean, S., Marshall, D., Pekarsky, Y., Hagan, J. P., Zanesi, N., Kaou, M., Stein, G. S., Lian, J. B., & Croce, C. M. (2007). Targeted deletion of Wwox reveals a tumor suppressor function. Proceedings of the National Academy of Sciences of the United States of America, 104(10), 3949-3954. https://doi.org/10.1073/pnas.0609783104

@article{1c50ec38fec84362abc17d8981536964,

title = "Targeted deletion of Wwox reveals a tumor suppressor function",

abstract = "The WW domain-containing oxidoreductase (WWOX) spans the second most common fragile site of the human genome, FRA16D, located at 16q23, and its expression is altered in several types of human cancer. We have previously shown that restoration of WWOX expression in cancer cells suppresses tumorigenicity. To investigate WWOX tumor suppressor function in vivo, we generated mice carrying a targeted deletion of the Wwox gene and monitored incidence of tumor formation. Osteosarcomas in juvenile Wwox-/- and lung papillary carcinoma in adult Wwox+/- mice occurred spontaneously. In addition, Wwox +/- mice develop significantly more ethyl nitrosourea-induced lung tumors and lymphomas in comparison to wild-type littermate mice. Intriguingly, these tumors still express Wwox protein, suggesting haploinsuffiency of WWOX itself is cancer predisposing. These results indicate that WWOX is a bona fide tumor suppressor.",

keywords = "Common fragile site, FHIT, Knockout, Lung cancer, Osteosarcoma",

author = "Aqeilan, \{Rami I.\} and Francesco Trapasso and Sadiq Hussain and Stefan Costinean and Dean Marshall and Yuri Pekarsky and Hagan, \{John P.\} and Nicola Zanesi and Mohamed Kaou and Stein, \{Gary S.\} and Lian, \{Jane B.\} and Croce, \{Carlo M.\}",

year = "2007",

month = mar,

day = "6",

doi = "10.1073/pnas.0609783104",

language = "אנגלית",

volume = "104",

pages = "3949--3954",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "10",

}

TY - JOUR

T1 - Targeted deletion of Wwox reveals a tumor suppressor function

AU - Aqeilan, Rami I.

AU - Trapasso, Francesco

AU - Hussain, Sadiq

AU - Costinean, Stefan

AU - Marshall, Dean

AU - Pekarsky, Yuri

AU - Hagan, John P.

AU - Zanesi, Nicola

AU - Kaou, Mohamed

AU - Stein, Gary S.

AU - Lian, Jane B.

AU - Croce, Carlo M.

PY - 2007/3/6

Y1 - 2007/3/6

N2 - The WW domain-containing oxidoreductase (WWOX) spans the second most common fragile site of the human genome, FRA16D, located at 16q23, and its expression is altered in several types of human cancer. We have previously shown that restoration of WWOX expression in cancer cells suppresses tumorigenicity. To investigate WWOX tumor suppressor function in vivo, we generated mice carrying a targeted deletion of the Wwox gene and monitored incidence of tumor formation. Osteosarcomas in juvenile Wwox-/- and lung papillary carcinoma in adult Wwox+/- mice occurred spontaneously. In addition, Wwox +/- mice develop significantly more ethyl nitrosourea-induced lung tumors and lymphomas in comparison to wild-type littermate mice. Intriguingly, these tumors still express Wwox protein, suggesting haploinsuffiency of WWOX itself is cancer predisposing. These results indicate that WWOX is a bona fide tumor suppressor.

AB - The WW domain-containing oxidoreductase (WWOX) spans the second most common fragile site of the human genome, FRA16D, located at 16q23, and its expression is altered in several types of human cancer. We have previously shown that restoration of WWOX expression in cancer cells suppresses tumorigenicity. To investigate WWOX tumor suppressor function in vivo, we generated mice carrying a targeted deletion of the Wwox gene and monitored incidence of tumor formation. Osteosarcomas in juvenile Wwox-/- and lung papillary carcinoma in adult Wwox+/- mice occurred spontaneously. In addition, Wwox +/- mice develop significantly more ethyl nitrosourea-induced lung tumors and lymphomas in comparison to wild-type littermate mice. Intriguingly, these tumors still express Wwox protein, suggesting haploinsuffiency of WWOX itself is cancer predisposing. These results indicate that WWOX is a bona fide tumor suppressor.

KW - Common fragile site

KW - FHIT

KW - Knockout

KW - Lung cancer

KW - Osteosarcoma

UR - https://www.scopus.com/pages/publications/34247273473

U2 - 10.1073/pnas.0609783104

DO - 10.1073/pnas.0609783104

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 17360458

AN - SCOPUS:34247273473

SN - 0027-8424

VL - 104

SP - 3949

EP - 3954

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 10

ER -

Targeted deletion of Wwox reveals a tumor suppressor function

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this