Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice

K.A. Loffler, C.A. Biondi, M.G. Gartside, M.M. Serewko-Auret, R. Duncan, I.D. Tonks, A.W. Mould, Paul Waring, H.K. Muller, G.F. Kay, N.K. Hayward

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    To identify possible genetic interactions between themechanisms of tumor suppression of menin and pRb, weintercrossed mice with targeted deletions of Men1 andRb1, and compared tumor development in cohorts ofanimals carrying single or dual mutations of these tumorsuppressorgenes. In mice lacking one copy of Men1,pancreatic islet and anterior pituitary adenomas arecommon. In animals lacking one copy of Rb1, intermediatepituitary and thyroid tumors occur at highfrequency, with less frequent development of pancreaticislet hyperplasia and parathyroid lesions. In mice heterozygousfor both Men1 and Rb1, pancreatic hyperplasiaand tumors of the intermediate pituitary and thyroidoccurred at high frequency. Serum measurements ofcalcium and glucose did not vary significantly betweengenotypic groups. Loss of heterozygosity at the Rb1 locuswas common in pituitary and thyroid tumors, whereas lossof menin was observed in pancreatic and parathyroidlesions. The tumor spectrum in the double heterozygoteswas a combination of pathologies seen in each of theindividual heterozygotes, without decrease in age of onset,indicating independent, non-additive effects of the twomutations. Together with the lack of increased tumorspectrum, this suggests that menin and pRbfunct ion in acommon pathway of tumor suppression.
    Original languageEnglish
    Pages (from-to)4009-4017
    JournalOncogene
    Volume26
    Issue number27
    DOIs
    Publication statusPublished - 2007

    Fingerprint

    Knockout Mice
    Pituitary Neoplasms
    Neoplasms
    Thyroid Gland
    Loss of Heterozygosity
    Heterozygote
    Islets of Langerhans
    Age of Onset
    Hyperplasia
    Ions
    Pathology
    Glucose
    Mutation
    Serum

    Cite this

    Loffler, K. A., Biondi, C. A., Gartside, M. G., Serewko-Auret, M. M., Duncan, R., Tonks, I. D., ... Hayward, N. K. (2007). Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice. Oncogene, 26(27), 4009-4017. https://doi.org/10.1038/sj.onc.1210163
    Loffler, K.A. ; Biondi, C.A. ; Gartside, M.G. ; Serewko-Auret, M.M. ; Duncan, R. ; Tonks, I.D. ; Mould, A.W. ; Waring, Paul ; Muller, H.K. ; Kay, G.F. ; Hayward, N.K. / Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice. In: Oncogene. 2007 ; Vol. 26, No. 27. pp. 4009-4017.
    @article{a3d4b9c1d32042858319eba80a15b5eb,
    title = "Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice",
    abstract = "To identify possible genetic interactions between themechanisms of tumor suppression of menin and pRb, weintercrossed mice with targeted deletions of Men1 andRb1, and compared tumor development in cohorts ofanimals carrying single or dual mutations of these tumorsuppressorgenes. In mice lacking one copy of Men1,pancreatic islet and anterior pituitary adenomas arecommon. In animals lacking one copy of Rb1, intermediatepituitary and thyroid tumors occur at highfrequency, with less frequent development of pancreaticislet hyperplasia and parathyroid lesions. In mice heterozygousfor both Men1 and Rb1, pancreatic hyperplasiaand tumors of the intermediate pituitary and thyroidoccurred at high frequency. Serum measurements ofcalcium and glucose did not vary significantly betweengenotypic groups. Loss of heterozygosity at the Rb1 locuswas common in pituitary and thyroid tumors, whereas lossof menin was observed in pancreatic and parathyroidlesions. The tumor spectrum in the double heterozygoteswas a combination of pathologies seen in each of theindividual heterozygotes, without decrease in age of onset,indicating independent, non-additive effects of the twomutations. Together with the lack of increased tumorspectrum, this suggests that menin and pRbfunct ion in acommon pathway of tumor suppression.",
    author = "K.A. Loffler and C.A. Biondi and M.G. Gartside and M.M. Serewko-Auret and R. Duncan and I.D. Tonks and A.W. Mould and Paul Waring and H.K. Muller and G.F. Kay and N.K. Hayward",
    year = "2007",
    doi = "10.1038/sj.onc.1210163",
    language = "English",
    volume = "26",
    pages = "4009--4017",
    journal = "Oncogene",
    issn = "0950-9232",
    publisher = "Nature Publishing Group",
    number = "27",

    }

    Loffler, KA, Biondi, CA, Gartside, MG, Serewko-Auret, MM, Duncan, R, Tonks, ID, Mould, AW, Waring, P, Muller, HK, Kay, GF & Hayward, NK 2007, 'Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice' Oncogene, vol. 26, no. 27, pp. 4009-4017. https://doi.org/10.1038/sj.onc.1210163

    Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice. / Loffler, K.A.; Biondi, C.A.; Gartside, M.G.; Serewko-Auret, M.M.; Duncan, R.; Tonks, I.D.; Mould, A.W.; Waring, Paul; Muller, H.K.; Kay, G.F.; Hayward, N.K.

    In: Oncogene, Vol. 26, No. 27, 2007, p. 4009-4017.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice

    AU - Loffler, K.A.

    AU - Biondi, C.A.

    AU - Gartside, M.G.

    AU - Serewko-Auret, M.M.

    AU - Duncan, R.

    AU - Tonks, I.D.

    AU - Mould, A.W.

    AU - Waring, Paul

    AU - Muller, H.K.

    AU - Kay, G.F.

    AU - Hayward, N.K.

    PY - 2007

    Y1 - 2007

    N2 - To identify possible genetic interactions between themechanisms of tumor suppression of menin and pRb, weintercrossed mice with targeted deletions of Men1 andRb1, and compared tumor development in cohorts ofanimals carrying single or dual mutations of these tumorsuppressorgenes. In mice lacking one copy of Men1,pancreatic islet and anterior pituitary adenomas arecommon. In animals lacking one copy of Rb1, intermediatepituitary and thyroid tumors occur at highfrequency, with less frequent development of pancreaticislet hyperplasia and parathyroid lesions. In mice heterozygousfor both Men1 and Rb1, pancreatic hyperplasiaand tumors of the intermediate pituitary and thyroidoccurred at high frequency. Serum measurements ofcalcium and glucose did not vary significantly betweengenotypic groups. Loss of heterozygosity at the Rb1 locuswas common in pituitary and thyroid tumors, whereas lossof menin was observed in pancreatic and parathyroidlesions. The tumor spectrum in the double heterozygoteswas a combination of pathologies seen in each of theindividual heterozygotes, without decrease in age of onset,indicating independent, non-additive effects of the twomutations. Together with the lack of increased tumorspectrum, this suggests that menin and pRbfunct ion in acommon pathway of tumor suppression.

    AB - To identify possible genetic interactions between themechanisms of tumor suppression of menin and pRb, weintercrossed mice with targeted deletions of Men1 andRb1, and compared tumor development in cohorts ofanimals carrying single or dual mutations of these tumorsuppressorgenes. In mice lacking one copy of Men1,pancreatic islet and anterior pituitary adenomas arecommon. In animals lacking one copy of Rb1, intermediatepituitary and thyroid tumors occur at highfrequency, with less frequent development of pancreaticislet hyperplasia and parathyroid lesions. In mice heterozygousfor both Men1 and Rb1, pancreatic hyperplasiaand tumors of the intermediate pituitary and thyroidoccurred at high frequency. Serum measurements ofcalcium and glucose did not vary significantly betweengenotypic groups. Loss of heterozygosity at the Rb1 locuswas common in pituitary and thyroid tumors, whereas lossof menin was observed in pancreatic and parathyroidlesions. The tumor spectrum in the double heterozygoteswas a combination of pathologies seen in each of theindividual heterozygotes, without decrease in age of onset,indicating independent, non-additive effects of the twomutations. Together with the lack of increased tumorspectrum, this suggests that menin and pRbfunct ion in acommon pathway of tumor suppression.

    U2 - 10.1038/sj.onc.1210163

    DO - 10.1038/sj.onc.1210163

    M3 - Article

    VL - 26

    SP - 4009

    EP - 4017

    JO - Oncogene

    JF - Oncogene

    SN - 0950-9232

    IS - 27

    ER -

    Loffler KA, Biondi CA, Gartside MG, Serewko-Auret MM, Duncan R, Tonks ID et al. Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice. Oncogene. 2007;26(27):4009-4017. https://doi.org/10.1038/sj.onc.1210163