Suppression of melanotroph carcinogenesis leads to accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas in Rb +/- mice

Zongxiang Zhou, Andrea Flesken-Nikitin, Corinna Levine, Elena N. Shmidt, Jessica P. Eng, Ekaterina Yu Nikitina, David M. Spencer, Alexander Yu Nikitin

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)787-796
Number of pages10
JournalCancer Research
Volume65
Issue number3
StatePublished - Feb 1 2005
Externally publishedYes

Fingerprint

Melanotrophs
Anterior Pituitary Gland
Carcinogenesis
Neoplasms
Melanocyte-Stimulating Hormones
Transgenic Mice
Intermediate Pituitary Gland
Retinoblastoma Genes
Medullary Thyroid cancer
Pro-Opiomelanocortin
Immunologic Tests
Cell Lineage
Cell Culture Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Zhou, Z., Flesken-Nikitin, A., Levine, C., Shmidt, E. N., Eng, J. P., Nikitina, E. Y., ... Nikitin, A. Y. (2005). Suppression of melanotroph carcinogenesis leads to accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas in Rb +/- mice. Cancer Research, 65(3), 787-796.

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 journalArticle

Zhou, Z, Flesken-Nikitin, A, Levine, C, Shmidt, EN, Eng, JP, Nikitina, EY, Spencer, DM & Nikitin, AY 2005, 'Suppression of melanotroph carcinogenesis leads to accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas in Rb +/- mice', Cancer Research, vol. 65, no. 3, pp. 787-796.
Zhou, Zongxiang ; Flesken-Nikitin, Andrea ; Levine, Corinna ; Shmidt, Elena N. ; Eng, Jessica P. ; Nikitina, Ekaterina Yu ; Spencer, David M. ; Nikitin, Alexander Yu. / Suppression of melanotroph carcinogenesis leads to accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas in Rb +/- mice. In: Cancer Research. 2005 ; Vol. 65, No. 3. pp. 787-796.
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