Thyroid hormone depletion inhibits astrocytoma proliferation via a p53-independent induction of p21 (WAF1/CIP1). Toms, S A, Hercbergs, A, Liu, J, Kondo, S, Barnett, G H, Casey, G, & Barna, B P Anticancer Research, 18(1A):289–293, February, 1998.
Thyroid hormone depletion inhibits astrocytoma proliferation via a p53-independent induction of p21 (WAF1/CIP1) [link]Paper  abstract   bibtex   
BACKGROUND Clinical hypothyroidism has been associated with prolonged survival in several types of malignancies, but the mechanism of this effect is unknown. MATERIAL AND METHODS In vitro studies of thyroid hormone depletion (via culture in medium containing 5% thyroid hormone-depleted fetal bovine serum (FBS)) were carried out using a human glioblastoma cell line (WITG3) which expresses a mutant, non-functional p53. RESULTS Thyroid hormone depletion inhibited WITG3 proliferation compared to control medium containing 5% euthyroid FBS. There was no evidence of apoptosis and viability was not compromised. Cell cycle analysis by flow cytometry indicated that thyroid hormone depletion accumulated WITG3 cells in G1, with fewer cells progressing into S than in euthyroid medium. By immunoblotting, p21 (WAF1/CIP1) was only slightly detectable in lysates from WITG3 cells grown in control euthyroid medium; however, in thyroid hormone-depleted FBS, a marked induction of p2 1 occurred which could be reversed by exogenous thyroid hormone CONCLUSIONS These data indicate that thyroid hormone depletion may cause a G, arrest in astrocytoma mediated by a p53-independent induction of p21 (WAF1/CIP1). Results suggest a mechanism which may explain the effect of hypothyroidism on suppression of tumor cell growth.
@article{toms_thyroid_1998,
	title = {Thyroid hormone depletion inhibits astrocytoma proliferation via a p53-independent induction of p21 ({WAF1}/{CIP1})},
	volume = {18},
	issn = {0250-7005},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/9568092},
	abstract = {BACKGROUND

Clinical hypothyroidism has been associated with prolonged survival in several types of malignancies, but the mechanism of this effect is unknown.


MATERIAL AND METHODS

In vitro studies of thyroid hormone depletion (via culture in medium containing 5\% thyroid hormone-depleted fetal bovine serum (FBS)) were carried out using a human glioblastoma cell line (WITG3) which expresses a mutant, non-functional p53.


RESULTS

Thyroid hormone depletion inhibited WITG3 proliferation compared to control medium containing 5\% euthyroid FBS. There was no evidence of apoptosis and viability was not compromised. Cell cycle analysis by flow cytometry indicated that thyroid hormone depletion accumulated WITG3 cells in G1, with fewer cells progressing into S than in euthyroid medium. By immunoblotting, p21 (WAF1/CIP1) was only slightly detectable in lysates from WITG3 cells grown in control euthyroid medium; however, in thyroid hormone-depleted FBS, a marked induction of p2 1 occurred which could be reversed by exogenous thyroid hormone


CONCLUSIONS

These data indicate that thyroid hormone depletion may cause a G, arrest in astrocytoma mediated by a p53-independent induction of p21 (WAF1/CIP1). Results suggest a mechanism which may explain the effect of hypothyroidism on suppression of tumor cell growth.},
	number = {1A},
	urldate = {2012-01-03},
	journal = {Anticancer Research},
	author = {Toms, S A and Hercbergs, A and Liu, J and Kondo, S and Barnett, G H and Casey, G and Barna, B P},
	month = feb,
	year = {1998},
	pmid = {9568092},
	keywords = {Apoptosis, Astrocytoma, Cell Cycle, Cell Division, Cell Survival, Cyclin-Dependent Kinase Inhibitor p21, Cyclins, DNA Fragmentation, Humans, Thyroid Hormones, Tumor Cells, Cultured},
	pages = {289--293},
}

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