Vitamin D3 administration induces nuclear p27 accumulation, restores differentiation, and reduces tumor burden in a mouse model of metastatic follicular thyroid cancer

Alan P B Dackiw, Shereen Ezzat, Ping Huang, Wei Liu, Sylvia L. Asa

Research output: Contribution to journalArticle

Abstract

We have previously demonstrated in vitro that 1α,25-dihydroxyvitamin D3 (calcitriol) treatment increases p27 expression and decreases cell proliferation in cultured thyroid carcinoma cell lines. We hypothesized that in vivo treatment with calcitriol would have a beneficial effect on thyroid carcinoma growth and progression. Five × 10 6 WRO (human thyroid follicular carcinoma derived) cells were implanted in the neck in 4- to 5-wk-old female SCID mice in an orthotopic xenograft model. Animals (n = 15) were treated ip three times a week for 21 d with 0.75 μg/kg calcitriol or vehicle. Mice were killed 21 d after tumor implantation, tumor volume was measured, and excised tumor tissue was examined by light microscopy and immunohistochemistry for p27 and thyroglobulin reactivity. Average tumor volume in control mice after 21 d of vehicle treatment was 2002 ± 207 mm 3 compared with a mean tumor volume of 1241 ± 115 mm 3 in animals receiving calcitriol, reflecting a 38% reduction in tumor volume size (P <0.003). Tumors from vehicle-treated animals demonstrated morphological features of epithelial malignancies with characteristics of insular carcinoma and multiple metastases to the lungs. Tumors excised from calcitriol-treated animals demonstrated signs of differentiation with restoration of thyroglobulin staining. This was associated with a marked accumulation of p27 immunoreactivity in the nuclear compartment. These studies demonstrate that in vivo calcitriol administration can effectively restore p27 accumulation in thyroid carcinoma cells, an effect associated with appreciably enhanced cellular differentiation, reduction in tumor burden, and prevention of metastatic growth.

Original languageEnglish (US)
Pages (from-to)5840-5846
Number of pages7
JournalEndocrinology
Volume145
Issue number12
DOIs
StatePublished - Dec 2004

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Calcitriol
Cholecalciferol
Tumor Burden
Thyroid Neoplasms
Thyroglobulin
Neoplasms
Follicular Adenocarcinoma
SCID Mice
Growth
Follicular Thyroid cancer
Heterografts
Microscopy
Neck
Therapeutics
Immunohistochemistry
Cell Proliferation
Staining and Labeling
Neoplasm Metastasis
Carcinoma
Light

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Vitamin D3 administration induces nuclear p27 accumulation, restores differentiation, and reduces tumor burden in a mouse model of metastatic follicular thyroid cancer. / Dackiw, Alan P B; Ezzat, Shereen; Huang, Ping; Liu, Wei; Asa, Sylvia L.

In: Endocrinology, Vol. 145, No. 12, 12.2004, p. 5840-5846.

Research output: Contribution to journalArticle

Dackiw, Alan P B ; Ezzat, Shereen ; Huang, Ping ; Liu, Wei ; Asa, Sylvia L. / Vitamin D3 administration induces nuclear p27 accumulation, restores differentiation, and reduces tumor burden in a mouse model of metastatic follicular thyroid cancer. In: Endocrinology. 2004 ; Vol. 145, No. 12. pp. 5840-5846.
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