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Cristina, C.; Díaz-Torga, G.S.; Goya, R.G.; Kakar, S.S.; Perez-Millán, M.I.; Passos, V.Q.; Giannella-Neto, D.; Bronstein, M.D.; Becu-Villalobos, D. "PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes" (2007) Molecular Cancer. 6
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Abstract:

Background: Pituitary tumor transforming gene (pttg) is a novel oncogene that is expressed at higher level in most of the tumors analyzed to date compared to normal tissues. Nevertheless, its expression in prolactinomas and its relation with the pituitary dopamine receptor 2 (D2R) are not well defined. We sought to determine the pituitary level of pttg in three different experimental models of prolactinomas with altered dopaminergic control of the pituitary: the dopaminergic D2R knockout female mouse, the estrogen-treated rat, and the senescent female rat. These three models shared the characteristics of increased pituitary weight, hyperprolactinemia, lactotrope hyperplasia and reduced or absent dopaminergic action at the pituitary level. We also studied samples from human macroprolactinomas, which were characterized as responsive or resistant to dopamine agonist therapy. Results: When compared to female wild-type mice, pituitaries from female D2R knockout mice had decreased PTTG concentration, while no difference in pttg mRNA level was found. In senescent rats no difference in pituitary PTTG protein expression was found when compared to young rats. But, in young female rats treated with a synthetic estrogen (Diethylstylbestrol, 20 mg) PTTG protein expression was enhanced (P = 0.029). Therefore, in the three experimental models of prolactinomas, pituitary size was increased and there was hyperprolactinemia, but PTTG levels followed different patterns. Patients with macroprolactinomas were divided in those in which dopaminergic therapy normalized or failed to normalize prolactin levels (responsive and resistant, respectively). When pituitary pttg mRNA level was analyzed in these macroprolactinomas, no differences were found. We next analyzed estrogen action at the pituitary by measuring pituitary estrogen receptor α levels. The D2R knockout female mice have low estrogen levels and in accordance, pituitary estrogen receptors were increased (P = 0.047). On the other hand, in senescent rats estrogen levels were slightly though not significantly higher, and estrogen receptors were similar between groups. The estrogen-treated rats had high pharmacological levels of the synthetic estrogen, and estrogen receptors were markedly lower than in controls (P < 0.0001). Finally, in patients with dopamine resistant or responsive prolactinomas no significant differences in estrogen receptor α levels were found. Therefore, pituitary PTTG was increased only if estrogen action was increased, which correlated with a decrease in pituitary estrogen receptor level. Conclusion: We conclude that PTTG does not correlate with prolactin levels or tumor size in animal models of prolactinoma, and its pituitary content is not related to a decrease in dopaminergic control of the lactotrope, but may be influenced by estrogen action at the pituitary level. Therefore it is increased only in prolactinomas generated by estrogen treatment, and not in prolactinomas arising from deficient dopamine control, or in dopamine resistant compared with dopamine responsive human prolactinomas. These results are important in the search for reliable prognostic indicators for patients with pituitary adenomas which will make tumor-specific therapy possible, and help to elucidate the poorly understood phenomenon of pituitary tumorigenesis. © 2007 Cristina et al; licensee BioMed Central Ltd.

Registro:

Documento: Artículo
Título:PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes
Autor:Cristina, C.; Díaz-Torga, G.S.; Goya, R.G.; Kakar, S.S.; Perez-Millán, M.I.; Passos, V.Q.; Giannella-Neto, D.; Bronstein, M.D.; Becu-Villalobos, D.
Filiación:Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, V. Obligado 2490, 1428 Buenos Aires, Argentina
Institute for Biochemical Research-Histology B, Faculty of Medicine, University of La Plata, La Plata, Argentina
Department of Medicine, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, United States
Division of Endocrinology and Metabolism, Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brazil
Laboratory for Cellular and Molecular Endocrinology (LIM 25), Hospital das Clinicas, University of Sao Paulo Medical School, Sao Paulo, Brazil
Palabras clave:dopamine receptor stimulating agent; estrogen derivative; estrogen receptor alpha; messenger RNA; oncoprotein; pituitary tumor transforming protein; prolactin; unclassified drug; aging; animal experiment; animal model; animal tissue; article; carcinogenesis; controlled study; correlation analysis; dopaminergic system; female; human; human tissue; hyperprolactinemia; hypophysis; hypophysis adenoma; mouse; nonhuman; organ weight; prognosis; prolactinoma; protein analysis; protein expression; rat; reliability; tumor volume; wild type; Adult; Animals; Antineoplastic Agents, Hormonal; Dopamine; Drug Resistance, Neoplasm; Estrogen Receptor alpha; Female; Humans; Lactotrophs; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Pituitary Neoplasms; Prolactinoma; Rats; Rats, Sprague-Dawley; Receptors, Dopamine; Animalia; Mus; Rattus
Año:2007
Volumen:6
DOI: http://dx.doi.org/10.1186/1476-4598-6-4
Título revista:Molecular Cancer
Título revista abreviado:Mol. Cancer
ISSN:14764598
CODEN:MCOAC
CAS:prolactin, 12585-34-1, 50647-00-2, 9002-62-4; Antineoplastic Agents, Hormonal; Estrogen Receptor alpha; Neoplasm Proteins; Receptors, Dopamine; pituitary tumor-transforming proteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14764598_v6_n_p_Cristina

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Citas:

---------- APA ----------
Cristina, C., Díaz-Torga, G.S., Goya, R.G., Kakar, S.S., Perez-Millán, M.I., Passos, V.Q., Giannella-Neto, D.,..., Becu-Villalobos, D. (2007) . PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes. Molecular Cancer, 6.
http://dx.doi.org/10.1186/1476-4598-6-4
---------- CHICAGO ----------
Cristina, C., Díaz-Torga, G.S., Goya, R.G., Kakar, S.S., Perez-Millán, M.I., Passos, V.Q., et al. "PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes" . Molecular Cancer 6 (2007).
http://dx.doi.org/10.1186/1476-4598-6-4
---------- MLA ----------
Cristina, C., Díaz-Torga, G.S., Goya, R.G., Kakar, S.S., Perez-Millán, M.I., Passos, V.Q., et al. "PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes" . Molecular Cancer, vol. 6, 2007.
http://dx.doi.org/10.1186/1476-4598-6-4
---------- VANCOUVER ----------
Cristina, C., Díaz-Torga, G.S., Goya, R.G., Kakar, S.S., Perez-Millán, M.I., Passos, V.Q., et al. PTTG expression in different experimental and human prolactinomas in relation to dopaminergic control of lactotropes. Mol. Cancer. 2007;6.
http://dx.doi.org/10.1186/1476-4598-6-4