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- Horvath, G, et al.
(författare)
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Characterization of an estradiol-independent but estradiol-responsive growth phenotype in a human endometrial adenocarcinoma heterotransplanted into nude mice
- 1992
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Ingår i: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 2:2, s. 101-106
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Tidskriftsartikel (refereegranskat)abstract
- The tumor growth phenotype was characterized in relation to concentration of circulating estradiol, estradiol receptor (ER) activation and progesterone receptor (PgR) induction. Ten tumor pieces from an ER and PgR positive human endometrial adenocarcinoma grown in non-oophorectomized nude mice for one year were randomly selected to grow during a preparation phase of 4 weeks either in oophorectomized nude mice - to adapt tumor growth to the absence of estradiol (group A), or in non-oophorectomized nude mice (group B). For the experimental phase, tumor pieces from each group were again randomly assigned to either of two subgroups (i.e., 4 subgroups in all): with estradiol treatment (subgroups A+ and B+), or without (subgroups A- and B-) as control subgroups. There were no differences in take rate or tumor growth rate between the control subgroups (A- vs. B-), indicating tumor growth to be estradiol-independent. The tumor was estradiol-sensitive, however, as tumor growth could be stimulated by estradiol. Despite its estradiol-independence of growth, the tumor's estradiol-binding capacity varied according to whether the host animals were oophorectomized or not; and despite the similar growth patterns during the experimental phase, the values of high affinty bound ER (ER activation) were greater for tumors grown in non-oophorectomized mice during the preparation phase than for those grown in oophorectomized mice. Thus, our findings show that an ovarain (estradiol) independent but responsive phenotype of tumor growth is present in human endometrial adenocarcinomas growing in nude mice. This growth phenotype may represent an intermediate state of tumor progression to hormone independence and resistance, which has hitherto been observed only in rodent tumors.
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| 2. |
- Horvath, G, et al.
(författare)
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Effect of estradiol on tumor growth, cell kinetics and p53 oncoprotein expression in human endometrial adenocarcinoma heterotransplanted into nude mice
- 1993
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Ingår i: In Vivo. - 0258-851X. ; 7:5, s. 451-456
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Tidskriftsartikel (refereegranskat)abstract
- To study the importance of estradiol concentrations in which tumors are growing to progression of tumor growth and cell kinetics, we have used a human tumor-nude mice model. In this model a human endometrial adenocarcinoma with estradiol independent but estradiol-responsive growth phenotype (i.e. the tumor was capable of growing in absence of estradiol but its growth could be stimulated by estradiol at the start of preparation phase) was examined. In the preparation phase pieces from this tumor were transplanted into nude mice, randomly divided into two groups, one with and one without estradiol treatment. After 18 months growth in these different hormone conditions the tumors were measured for p53 protein expression and pieces from both these groups were again transplanted into oophorectomized nude mice, each group being randomly allocated to two subgroups, one with and one without estradiol treatment (experimental phase). Tumor growth was measured during the experimental phase, whereas cell kinetic parameters and steroid receptor concentrations were analyzed after the experimental phase. Our findings indicate that progression of the growth phenotype is independent of estradiol conditions in which human endometrial adenocarcinomas are grown. Long-term growth in estradiol-poor conditions results in estradiol resistance of the cell cycle, probably accompanied by overexpression of the p53 protein. Tumor growth in estradiol-rich conditions, however, may protect, at least to some extent, the same tumor, which retains higher sensitivity of cell proliferation to estradiol and normal production of the p53 protein despite progressive changes in growth regulation.
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| 3. |
- Horvath, G, et al.
(författare)
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Estradiol induced changes in tumor growth and steroid receptor content in a heterotransplanted human endometrial adenocarcinoma
- 1991
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Ingår i: In Vivo. - 0258-851X. ; 5:4, s. 401-406
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Tidskriftsartikel (refereegranskat)abstract
- To study the importance of estrogen availability to growth pattern and other tumor characteristic such as estrogen receptor (ER) and progesterone receptor (PgR) content and histopathology, we have used a human tumor-nude mouse model, in which an ER- and PgR-positive and estradiol-sensitive (stimulated) human endometrial adenocarcinoma was heterotransplanted and serially passed in female (non-oophorectomized) nude mice over a period of one year. Pieces from this tumor were transplanted into oophorectomized nude mice, randomly divided into two groups, one with and one without estradiol treatment (preparation phase). After four weeks, pieces from both these groups were again transplanted into oophorectomized nude mice, each group being randomly allocated to two subgroups, one with and one without estradiol treatment (experimental phase). Tumor growth was measured during the experimental phase, whereas both ER and PgR content and histopathology were analyzed after the experimental phase. Our findings indicate that even short-term growth under estradiol-poor conditions can trigger such progressive changes as reduced steroid receptor content, development of a less differentiated tumor and tendency to enhanced tumor growth. On the other hand, estradiol-rich conditions enhanced ER activation, PgR induction and tumor differentiation in the same tumor line. The estrogenic conditions under which a tumor grows may thus be crucial determinants of tumor progression.
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| 4. |
- Horvath, G, et al.
(författare)
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Growth interaction between different tumor populations in human endometrial adenocarcinoma growing in nude mice
- 1993
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Ingår i: In Vivo. - 0258-851X. ; 7:6A, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- In these studies of tumor cell growth interaction we have used two tumors differing from each other in sensitivity to estradiol, transplanted to opposite sites of the same nude mice. In the first experiment we found that the growth of an estradiol-sensitive tumor may be delayed by the presence of an estradiol-resistant tumor in the same animal. Although the growth pattern was changed, proliferative activity, as reflected in the S-phase fraction measured by flow cytometry, and the steroid receptor concentrations were unchanged. Increase of circulating estradiol, however, protects the estradiol-sensitive population from this down-regulation of growth. Findings in a second experiment suggest that this growth delay is probably caused by changes such as decrease in labelling index, increase of non BrdU-incorporating cells in the S-phase, and cell loss in estradiol-sensitive tumors. We concluded that the estradiol-resistant tumor population may secrete some factor(s) acting as endocrine product(s) which may delay the growth of estradiol-sensitive cell populations when the tumors are grown in an estradiol-poor environment. If our model also represents interactions between tumor subpopulations within a single tumor, these findings may have implications for our understanding of the biology of tumor progression in some hormone-related human tumors.
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| 5. |
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| 6. |
- Horvath, G, et al.
(författare)
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Progression of human endometrial adenocarcinoma heterotransplanted into nude mice from hormone-sensitive to hormone resistant growth
- 1991
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Ingår i: In Vivo. - 0258-851X. ; 5:2, s. 185-190
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Tidskriftsartikel (refereegranskat)abstract
- We have used a human tumor nude mouse model involving heterotransplantation and serial passage of an estrogen receptor (ER) positive, progesterone receptor (PgR) negative human endometrial adenocarcinoma. The effects of estradiol treatment on tumor growth, ER activation and PgR induction were investigated two and four years after heterotransplantation. In Experiment I, two years after initial heterotransplantation, tumor growth and proliferative rate showed a dose-related decrease, ER was activated by estradiol treatment (measured through an increased amount of ER bound with high affinity to nuclear element(s) (ERhs) and PgR was induced. Two years later (Experiment II), the amount of ER1s (ER measured in cytosolic fraction) as well as of ERhs was lower than at the beginning of Experiment I. ER could again be activated by estradiol treatment and PgR was also induced. However, in this experiment no effect either of tumor growth or of proliferative rate was observed during the estradiol treatment. Our study therefore indicates that an estrogen non-sensitive growth can develop during serial passages in intact, non-treated female nude mice, although the capacity for ER activation and PgR induction is maintained.
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