Artículo

Huhtaniemi, I.; Rulli, S.; Ahtiainen, P.; Poutanen, M. "Multiple sites of tumorigenesis in transgenic mice overproducing hCG" (2005) Molecular and Cellular Endocrinology. 234(1-2):117-126
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Abstract:

We have produced transgenic (TG) mice expressing under the ubiquitin C promoter either the glycoprotein hormone common α-subunit (Cα) or human chorionic gonadotropin (hCG) β-subunit. Cα overexpression alone had no phenotypic effect, but the hCGβ expressing females, presenting with moderately elevated levels of bioactive LH/hCG, due to dimerization of the TG hCGβ with endogenous Cα, developed multiple gonadal and extragonadal neoplasias. Crosses of the Cα and hCGβ mice (hCGαβ) had >1000-fold elevated hCG levels, due to ubiquitous transgene expression, and presented with more aggressive tumour formation. The ovaries displayed initially strong luteinisation of all somatic cell types, leading to formation of luteomas, and subsequently to germ cell tumours (teratomas). The pituitary glands of TG females were massively enlarged, up to >100 mg, developing macroprolactinomas with very high prolactin (PRL) production. This endocrine response probably induced breast cancers in the mice. In contrast to the females, similar high levels of hCG in male mice had only marginal effects in adulthood, with slight Leydig cell hyperplasia and atrophy in the seminiferous epithelium. However, clear Leydig cell adenomas were observed in postnatal mice, apparently originating from fetal Leydig cells. In conclusion, these studies demonstrate marked tumorigenic effects of supraphysiological hCG levels in female mice, but clear resistance to similar changes in males. The extragonadal tumours were induced by hCG stimulated aberrant ovarian endocrine function, rather than by direct hCG action, because gonadectomy prevented all extragonadal phenotypes despite persistent hCG elevation. The phenotypes of the TG mice apparently represent exaggerated responses to hCG/LH and/or gonadal steroids. It remains to be explored to what extent they simulate respective responses in humans to pathophysiological elevation of the same hormones. © 2005 Elsevier Ireland Ltd. All rights reserved.

Registro:

Documento: Artículo
Título:Multiple sites of tumorigenesis in transgenic mice overproducing hCG
Autor:Huhtaniemi, I.; Rulli, S.; Ahtiainen, P.; Poutanen, M.
Filiación:Department of Physiology, University of Turku, Kiinamyllynkatu 10, 20540 Turku, Finland
Inst. of Repro. and Devmtl. Biology, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, United Kingdom
Inst. of Biol. and Exp. Medicine, CONICET, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:Choriongonadotropin; Leydig cell adenoma; Luteoma; Mammary tumours; Ovarian tumours; Pituitary tumours; Prolactinoma; Teratoma; Transgenic mice; chorionic gonadotropin; luteinizing hormone; prolactin; protein subunit; sex hormone; ubiquitin C; adulthood; alpha chain; blood level; breast carcinoma; breast tumor; cancer localization; carcinogenesis; cell type; conference paper; gene overexpression; germ cell tumor; gonadectomy; hormone release; human; hyperplasia; hypophysis; hypophysis tumor; Leydig cell; luteinization; luteoma; mammary gland; nonhuman; ovary teratoma; ovary tumor; pathophysiology; perinatal period; phenotype; priority journal; prolactinoma; protein expression; seminiferous tubule epithelium; somatic cell; transgene; transgenic mouse
Año:2005
Volumen:234
Número:1-2
Página de inicio:117
Página de fin:126
DOI: http://dx.doi.org/10.1016/j.mce.2004.10.013
Título revista:Molecular and Cellular Endocrinology
Título revista abreviado:Mol. Cell. Endocrinol.
ISSN:03037207
CODEN:MCEND
CAS:chorionic gonadotropin, 9002-61-3; luteinizing hormone, 39341-83-8, 9002-67-9; prolactin, 12585-34-1, 50647-00-2, 9002-62-4; ubiquitin C, 151821-62-4
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03037207_v234_n1-2_p117_Huhtaniemi

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Citas:

---------- APA ----------
Huhtaniemi, I., Rulli, S., Ahtiainen, P. & Poutanen, M. (2005) . Multiple sites of tumorigenesis in transgenic mice overproducing hCG. Molecular and Cellular Endocrinology, 234(1-2), 117-126.
http://dx.doi.org/10.1016/j.mce.2004.10.013
---------- CHICAGO ----------
Huhtaniemi, I., Rulli, S., Ahtiainen, P., Poutanen, M. "Multiple sites of tumorigenesis in transgenic mice overproducing hCG" . Molecular and Cellular Endocrinology 234, no. 1-2 (2005) : 117-126.
http://dx.doi.org/10.1016/j.mce.2004.10.013
---------- MLA ----------
Huhtaniemi, I., Rulli, S., Ahtiainen, P., Poutanen, M. "Multiple sites of tumorigenesis in transgenic mice overproducing hCG" . Molecular and Cellular Endocrinology, vol. 234, no. 1-2, 2005, pp. 117-126.
http://dx.doi.org/10.1016/j.mce.2004.10.013
---------- VANCOUVER ----------
Huhtaniemi, I., Rulli, S., Ahtiainen, P., Poutanen, M. Multiple sites of tumorigenesis in transgenic mice overproducing hCG. Mol. Cell. Endocrinol. 2005;234(1-2):117-126.
http://dx.doi.org/10.1016/j.mce.2004.10.013