The expression of AIP-related molecules in elucidation of cellular pathways in pituitary adenomas

Elina Heliövaara, Anniina Raitila, Virpi Launonen, Anders Paetau, Johanna Arola, Heli Lehtonen, Timo Sane, Robert J Weil, Outi Vierimaa, Pasi Salmela, Karoliina Tuppurainen, Markus Mäkinen, Lauri A Aaltonen, Auli Karhu

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    Sammanfattning

    "Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene predispose to the development of pituitary adenomas. Here, we characterized AIP mutation positive (AIPmut+) and AIP mutation negative (AlPmut-) pituitary adenomas by immmohistochemistry. The expressions of the AIP-related proteins aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), cyclin-dependent kinase inhibitor 1B encoding p27(Kip1), and hypoxia-inducible factor I-a were examined in 14 AIPmut+ and 53 AlPmut- pituitary adenomas to detect possible expression differences. In addition, the expression of CD34, an endothelial and hematopoietic stem cell marker, was analyzed. We found ARNT to be less frequently expressed inAIPmut+ pituitary adenomas (P = 0.001), suggesting that AIP regulates the ARNT levels. AIP small interfering RNA-treated HeLa, ffEK293, or Aip-null mouse embryonic fibroblast cells did not show lowered expression of ARNT. Instead, in the pituitary adenoma cell line GH3, Aip silencing caused a partial reduction of Arnt and a clear increase in cell proliferation. We also observed a trend for increased expression of nuclear AHR in AIPmut+ samples, although the difference was not statistically significant (P = 0.06). The expressions of p27(Kip1), hypoxia-inducible factor I-a, or CD34 did not differ between tumor types. The present study shows that the expression of ARNT protein is significantly reduced in AIPmut+ tumors. We suggest that the down-regulation of ARNT may be connected to an imbalance in AHR/ARNT complex formation arising from aberrant cAMP signaling. (Am J Pathol 2009, 175:2501-2507; DOI: 10.2353.ajpath.2009.081131)"
    Originalspråkengelska
    TidskriftThe American Journal of Pathology
    Volym175
    Utgåva6
    Sidor (från-till)2501-2507
    Antal sidor7
    ISSN0002-9440
    DOI
    StatusPublicerad - 2009
    MoE-publikationstypA1 Tidskriftsartikel-refererad

    Vetenskapsgrenar

    • 311 Basmedicin

    Citera det här

    Heliövaara, Elina ; Raitila, Anniina ; Launonen, Virpi ; Paetau, Anders ; Arola, Johanna ; Lehtonen, Heli ; Sane, Timo ; Weil, Robert J ; Vierimaa, Outi ; Salmela, Pasi ; Tuppurainen, Karoliina ; Mäkinen, Markus ; Aaltonen, Lauri A ; Karhu, Auli. / The expression of AIP-related molecules in elucidation of cellular pathways in pituitary adenomas. I: The American Journal of Pathology. 2009 ; Vol. 175, Nr. 6. s. 2501-2507.
    @article{10e6c1daf45a4755b8325e92796e55fd,
    title = "The expression of AIP-related molecules in elucidation of cellular pathways in pituitary adenomas",
    abstract = "{"}Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene predispose to the development of pituitary adenomas. Here, we characterized AIP mutation positive (AIPmut+) and AIP mutation negative (AlPmut-) pituitary adenomas by immmohistochemistry. The expressions of the AIP-related proteins aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), cyclin-dependent kinase inhibitor 1B encoding p27(Kip1), and hypoxia-inducible factor I-a were examined in 14 AIPmut+ and 53 AlPmut- pituitary adenomas to detect possible expression differences. In addition, the expression of CD34, an endothelial and hematopoietic stem cell marker, was analyzed. We found ARNT to be less frequently expressed inAIPmut+ pituitary adenomas (P = 0.001), suggesting that AIP regulates the ARNT levels. AIP small interfering RNA-treated HeLa, ffEK293, or Aip-null mouse embryonic fibroblast cells did not show lowered expression of ARNT. Instead, in the pituitary adenoma cell line GH3, Aip silencing caused a partial reduction of Arnt and a clear increase in cell proliferation. We also observed a trend for increased expression of nuclear AHR in AIPmut+ samples, although the difference was not statistically significant (P = 0.06). The expressions of p27(Kip1), hypoxia-inducible factor I-a, or CD34 did not differ between tumor types. The present study shows that the expression of ARNT protein is significantly reduced in AIPmut+ tumors. We suggest that the down-regulation of ARNT may be connected to an imbalance in AHR/ARNT complex formation arising from aberrant cAMP signaling. (Am J Pathol 2009, 175:2501-2507; DOI: 10.2353.ajpath.2009.081131){"}",
    keywords = "311 Basic medicine",
    author = "Elina Heli{\"o}vaara and Anniina Raitila and Virpi Launonen and Anders Paetau and Johanna Arola and Heli Lehtonen and Timo Sane and Weil, {Robert J} and Outi Vierimaa and Pasi Salmela and Karoliina Tuppurainen and Markus M{\"a}kinen and Aaltonen, {Lauri A} and Auli Karhu",
    year = "2009",
    doi = "10.2353/ajpath.2009.081131",
    language = "English",
    volume = "175",
    pages = "2501--2507",
    journal = "The American Journal of Pathology",
    issn = "0002-9440",
    publisher = "EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC",
    number = "6",

    }

    Heliövaara, E, Raitila, A, Launonen, V, Paetau, A, Arola, J, Lehtonen, H, Sane, T, Weil, RJ, Vierimaa, O, Salmela, P, Tuppurainen, K, Mäkinen, M, Aaltonen, LA & Karhu, A 2009, 'The expression of AIP-related molecules in elucidation of cellular pathways in pituitary adenomas', The American Journal of Pathology, vol. 175, nr. 6, s. 2501-2507. https://doi.org/10.2353/ajpath.2009.081131

    The expression of AIP-related molecules in elucidation of cellular pathways in pituitary adenomas. / Heliövaara, Elina; Raitila, Anniina; Launonen, Virpi; Paetau, Anders; Arola, Johanna; Lehtonen, Heli; Sane, Timo; Weil, Robert J; Vierimaa, Outi; Salmela, Pasi; Tuppurainen, Karoliina; Mäkinen, Markus; Aaltonen, Lauri A; Karhu, Auli.

    I: The American Journal of Pathology, Vol. 175, Nr. 6, 2009, s. 2501-2507.

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    TY - JOUR

    T1 - The expression of AIP-related molecules in elucidation of cellular pathways in pituitary adenomas

    AU - Heliövaara, Elina

    AU - Raitila, Anniina

    AU - Launonen, Virpi

    AU - Paetau, Anders

    AU - Arola, Johanna

    AU - Lehtonen, Heli

    AU - Sane, Timo

    AU - Weil, Robert J

    AU - Vierimaa, Outi

    AU - Salmela, Pasi

    AU - Tuppurainen, Karoliina

    AU - Mäkinen, Markus

    AU - Aaltonen, Lauri A

    AU - Karhu, Auli

    PY - 2009

    Y1 - 2009

    N2 - "Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene predispose to the development of pituitary adenomas. Here, we characterized AIP mutation positive (AIPmut+) and AIP mutation negative (AlPmut-) pituitary adenomas by immmohistochemistry. The expressions of the AIP-related proteins aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), cyclin-dependent kinase inhibitor 1B encoding p27(Kip1), and hypoxia-inducible factor I-a were examined in 14 AIPmut+ and 53 AlPmut- pituitary adenomas to detect possible expression differences. In addition, the expression of CD34, an endothelial and hematopoietic stem cell marker, was analyzed. We found ARNT to be less frequently expressed inAIPmut+ pituitary adenomas (P = 0.001), suggesting that AIP regulates the ARNT levels. AIP small interfering RNA-treated HeLa, ffEK293, or Aip-null mouse embryonic fibroblast cells did not show lowered expression of ARNT. Instead, in the pituitary adenoma cell line GH3, Aip silencing caused a partial reduction of Arnt and a clear increase in cell proliferation. We also observed a trend for increased expression of nuclear AHR in AIPmut+ samples, although the difference was not statistically significant (P = 0.06). The expressions of p27(Kip1), hypoxia-inducible factor I-a, or CD34 did not differ between tumor types. The present study shows that the expression of ARNT protein is significantly reduced in AIPmut+ tumors. We suggest that the down-regulation of ARNT may be connected to an imbalance in AHR/ARNT complex formation arising from aberrant cAMP signaling. (Am J Pathol 2009, 175:2501-2507; DOI: 10.2353.ajpath.2009.081131)"

    AB - "Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene predispose to the development of pituitary adenomas. Here, we characterized AIP mutation positive (AIPmut+) and AIP mutation negative (AlPmut-) pituitary adenomas by immmohistochemistry. The expressions of the AIP-related proteins aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), cyclin-dependent kinase inhibitor 1B encoding p27(Kip1), and hypoxia-inducible factor I-a were examined in 14 AIPmut+ and 53 AlPmut- pituitary adenomas to detect possible expression differences. In addition, the expression of CD34, an endothelial and hematopoietic stem cell marker, was analyzed. We found ARNT to be less frequently expressed inAIPmut+ pituitary adenomas (P = 0.001), suggesting that AIP regulates the ARNT levels. AIP small interfering RNA-treated HeLa, ffEK293, or Aip-null mouse embryonic fibroblast cells did not show lowered expression of ARNT. Instead, in the pituitary adenoma cell line GH3, Aip silencing caused a partial reduction of Arnt and a clear increase in cell proliferation. We also observed a trend for increased expression of nuclear AHR in AIPmut+ samples, although the difference was not statistically significant (P = 0.06). The expressions of p27(Kip1), hypoxia-inducible factor I-a, or CD34 did not differ between tumor types. The present study shows that the expression of ARNT protein is significantly reduced in AIPmut+ tumors. We suggest that the down-regulation of ARNT may be connected to an imbalance in AHR/ARNT complex formation arising from aberrant cAMP signaling. (Am J Pathol 2009, 175:2501-2507; DOI: 10.2353.ajpath.2009.081131)"

    KW - 311 Basic medicine

    U2 - 10.2353/ajpath.2009.081131

    DO - 10.2353/ajpath.2009.081131

    M3 - Article

    VL - 175

    SP - 2501

    EP - 2507

    JO - The American Journal of Pathology

    JF - The American Journal of Pathology

    SN - 0002-9440

    IS - 6

    ER -