| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
A rat pituitary tumor sub-line MtT/E-2 was established from a rat pituitary tumor cell line MtT/E.Its growth was found to depend on the presence of estradiol (E_2) in culture media at 10^<-13>-10^<-9> M, whereas the original cell line MtT/E proliferated autonomously. The recently discovered PTTG (pituitary tumor transforming gene) is highly expressed in this cell line, although not regulated by E_2. On the other hand, E_2 induced c-myc and cyclin D1 proteins in MtT/E-2, which contains a lot (220 fmol/mg protein) of estrogen receptor demonstrated by RT-PCR analysis to be predominantly of a type. MtT/E-2 secretes growth hormone which is, interestingly, regulated by retinoic acid and dexamethasone rather than thyroid hormones.
Recently a novel oncogene, PTTG (pituitary tumor transforming gene) was isolated from a rat pituitary tumor cell line and it appeared to be correlated with pituitary tumorigenesis. In the rat, estrogen (E_2) is known to induce anterior pituitary hyperplasia. The effects of E_2, however, vary greatly among rat strains. Therefore we examined the expression of PTTG and its E_2 regulation in different stains of rats. Four week-old female F344, Wistar, Brown-Norway and Donryu rats were ovariectomied and a pellet containing 10 mg of E_2 was given s.c. Total RNA was isolated from the pituitary gland and PTTG mRNA was measured with a competitive RT-PCR technique. The F344 strain was the most susceptible for E_2 induce pituitary tumorigenesis followed by Wistar and BN, while no increases in pituitary weight were noted in Donryu rats. PTTG mRNA in the gland was induced by E_2 within 48-72 hours in F344 and Wistar but not in Brown-Norway or Donryu strains. These data suggest that PTTG expression is at least in part responsible to the strain difference of E_2 induced pituitary tumorigenesis.
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