Adrenocortical tumorigenesis in transgenic mice: the role of luteinizing hormone receptor and transcription factors GATA-4 and GATA-61.
摘要:
Transgenic (TG) , bearing the T-antigen (Tag) under a 6-kb fragment of the inhibin alpha-subunit promoter (inhalpha), develop gonadal of granulosa or Leydig cell origin with 100% penetrance by the age of 5-7 months. When these TG were gonadectomized prepubertally, between 21-25 days of life, were observed in each by the age of 5-7 months. No were detected in any intact TG, gonadectomized or intact or control non-TG littermates. The appeared to originate from the X-zone of the adrenal cortex. If functional gonadectomy was induced by treatment or by cross-breeding of the TG into hypogonadotropic hpg genetic background, neither gonadal nor adrenal appeared. This prompted a hypothesis that in inhalpha/Tag TG is related to elevated gonadotropin , which is the most obvious difference between the surgical and functional gonadectomy models. The and a cell line (Calpha1) derived from them, was found to express (), but no , and hCG treatment stimulated their proliferation. No was found in the adrenal glands. On the basis of this it was suggested that expression of the potent oncogene T-antigen, allow LH in adrenocortical cells to function as a promoter, and induction of high level functional expression in . Given the induction of expression and regulation of the -4 and -6 zinc finger family of factors in the gonads by gonadotropins, it was in our interest to explore their expression in the adrenals. We utilized the inalpha/Tag TG model and pathological adrenal samples to explore the role of -4 and -6 in adrenocortical . Abundant -6 mRNA expression was found in normal control adrenal cortex during , whereas -4 mRNA was undetectable. In striking contrast to this, -6 was absent from , while -4 mRNA expression was dramatically upregulated in the as well as in . Taken together, these results suggest different roles for -4 and -6 in the adrenal gland, and implicate -4 in adrenal expression and . Immunohistochemical detection of -4 may serve as a useful marker in differential diagnosis of . In addition, the inhalpha/Tag TG model will be helpful for exploring the molecular mechanisms underlying adrenocortical , ectopic expression in adrenals and the -4/interaction that is related to adrenal in TG .
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关键词:
Animals Mice Adrenal Cortex Neoplasms Disease Models, Animal Inhibins Transcription Factors DNA-Binding Proteins Recombinant Fusion Proteins Receptors, LH Antigens, Polyomavirus Transforming
DOI:
10.1016/j.phymed.2009.08.007
被引量:
年份:
2001
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