Abstract
Mice with a single copy of the retinoblastoma gene (Rb+/-) develop a syndrome of multiple neuroendocrine neoplasia. They usually succumb to fast-growing, Rb-deficient melanotropli tumors of the pituitary intermediate lobe, which are extremely rare in humans. Thus, full assessment of Rb role in other, more relevant to human pathology, neoplasms is complicated. To prevent melanotroph neoplasia while preserving spontaneous carcinogenesis in other types of cells, we have prepared transgenic mice in which 770-bp fragment of pro-opiomelanocortin promoter directs expression of the human BB gene to melanotrophs (TgPOMC-BB). In three independent lines, transgenic mice crossed to Rb+/- background are devoid of melanotroph tumors but develop the asual spectrum of other neoplasms. Interestingly, abrogation of melanotroph carcinogenesis results in accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas. A combination of immunologic tests, cell culture studies, and tumorigenicity assays indicates that α-melanocyte-stimulating hormone, which is overproduced by melanotroph tumors, attenuates neoplastic progression by decreasing cell proliferation and inducing apoptosis. Taken together, we show that cell lineage-specific complementation of Rb function can be successfully used for refining available models of stochastic carcinogenesis and identify α-melanocyte-stimulating hormone as a potential attenuating factor during progression of neuroendocrine neoplasms.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 787-796 |
| Number of pages | 10 |
| Journal | Cancer Research |
| Volume | 65 |
| Issue number | 3 |
| State | Published - Feb 1 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Suppression of melanotroph carcinogenesis leads to accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas in Rb +/- mice. / Zhou, Zongxiang; Flesken-Nikitin, Andrea; Levine, Corinna; Shmidt, Elena N.; Eng, Jessica P.; Nikitina, Ekaterina Yu; Spencer, David M.; Nikitin, Alexander Yu.
In: Cancer Research, Vol. 65, No. 3, 01.02.2005, p. 787-796.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Suppression of melanotroph carcinogenesis leads to accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas in Rb +/- mice
AU - Zhou, Zongxiang
AU - Flesken-Nikitin, Andrea
AU - Levine, Corinna
AU - Shmidt, Elena N.
AU - Eng, Jessica P.
AU - Nikitina, Ekaterina Yu
AU - Spencer, David M.
AU - Nikitin, Alexander Yu
PY - 2005/2/1
Y1 - 2005/2/1
N2 - Mice with a single copy of the retinoblastoma gene (Rb+/-) develop a syndrome of multiple neuroendocrine neoplasia. They usually succumb to fast-growing, Rb-deficient melanotropli tumors of the pituitary intermediate lobe, which are extremely rare in humans. Thus, full assessment of Rb role in other, more relevant to human pathology, neoplasms is complicated. To prevent melanotroph neoplasia while preserving spontaneous carcinogenesis in other types of cells, we have prepared transgenic mice in which 770-bp fragment of pro-opiomelanocortin promoter directs expression of the human BB gene to melanotrophs (TgPOMC-BB). In three independent lines, transgenic mice crossed to Rb+/- background are devoid of melanotroph tumors but develop the asual spectrum of other neoplasms. Interestingly, abrogation of melanotroph carcinogenesis results in accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas. A combination of immunologic tests, cell culture studies, and tumorigenicity assays indicates that α-melanocyte-stimulating hormone, which is overproduced by melanotroph tumors, attenuates neoplastic progression by decreasing cell proliferation and inducing apoptosis. Taken together, we show that cell lineage-specific complementation of Rb function can be successfully used for refining available models of stochastic carcinogenesis and identify α-melanocyte-stimulating hormone as a potential attenuating factor during progression of neuroendocrine neoplasms.
AB - Mice with a single copy of the retinoblastoma gene (Rb+/-) develop a syndrome of multiple neuroendocrine neoplasia. They usually succumb to fast-growing, Rb-deficient melanotropli tumors of the pituitary intermediate lobe, which are extremely rare in humans. Thus, full assessment of Rb role in other, more relevant to human pathology, neoplasms is complicated. To prevent melanotroph neoplasia while preserving spontaneous carcinogenesis in other types of cells, we have prepared transgenic mice in which 770-bp fragment of pro-opiomelanocortin promoter directs expression of the human BB gene to melanotrophs (TgPOMC-BB). In three independent lines, transgenic mice crossed to Rb+/- background are devoid of melanotroph tumors but develop the asual spectrum of other neoplasms. Interestingly, abrogation of melanotroph carcinogenesis results in accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas. A combination of immunologic tests, cell culture studies, and tumorigenicity assays indicates that α-melanocyte-stimulating hormone, which is overproduced by melanotroph tumors, attenuates neoplastic progression by decreasing cell proliferation and inducing apoptosis. Taken together, we show that cell lineage-specific complementation of Rb function can be successfully used for refining available models of stochastic carcinogenesis and identify α-melanocyte-stimulating hormone as a potential attenuating factor during progression of neuroendocrine neoplasms.
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M3 - Article
VL - 65
SP - 787
EP - 796
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 3
ER -