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Physiopathology of somatolactotroph cells: from transduction mechanisms to cotargeting therapy
Author(s) -
Cuny Thomas,
Gerard Corinne,
Saveanu Alexandru,
Barlier Anne,
Enjalbert Alain
Publication year - 2011
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2010.05924.x
Subject(s) - somatostatin receptor , somatostatin , signal transduction , somatostatin receptor 2 , cancer research , kinase , receptor tyrosine kinase , pi3k/akt/mtor pathway , receptor , microbiology and biotechnology , biology , tyrosine kinase , chemistry , endocrinology , biochemistry
In pituitary somatolactotroph cells, G protein–coupled receptors and receptor tyrosine kinases binding their specific ligands trigger an enzymatic cascade that converges to MAP kinase activation in the subcellular compartment. Different signaling pathways, such as AC/cAMP/PKA and PI3K/Akt pathways, interact with MAP kinase to regulate key physiological functions, such as hormonal secretion and cell proliferation. Abnormalities affecting these signaling pathways have been identified as preponderant factors of pituitary tumorigenesis. In addition to trans‐sphenoidal surgery, somatostatin analogs are used to control hormonal hypersecretion in GH‐secreting adenomas. However, a subset of these tumors remains uncontrolled with these treatFments, calling for new therapeutic approaches. In these cases, novel multivalent somatostatin analogs or new somatostatin–dopamine chimeric molecules could be of interest. Another attractive therapeutic approach may be to use one or several inhibitors acting downstream in the signaling pathway, such as mammalian target of rapamycin inhibitor. Cotargeting therapy and gene therapy are promising tools for these problematic pituitary tumors.