Abstract C146: In human lung carcinoma cells that contain estrogen receptor-α(ER), thyroid hormone-induced proliferation initiated at an integrin requires ER.

Abstract

Abstract We examined the molecular basis of thyroid hormone-induced proliferation of two estrogen receptor-α (ER)-expressing human lung cancer cell lines, non-small cell carcinoma NCI-H522 and small cell carcinoma NCI-H510A. At a physiologic total L-thyroxine (T4) concentration (10[−7] M) and supraphysiologic 3,5,3'-triiodo-L-thyronine (T3) levels, thyroid hormone significantly increased proliferating cell nuclear antigen (PCNA) content of both cell lines. Neutralizing antibody to integrin αvβ3 and integrin-binding Arg-Gly-Asp (RGD) peptide inhibited cell proliferation stimulated by thyroid hormone. Tetraiodothyroacetic acid (tetrac) blocks binding of T4 and T3 to the hormone receptor on αvβ3 and inhibited thyroid hormone-induced cancer cell proliferation. Thus, the thyroid hormone effect is initiated nongenomically at the cell surface thyroid hormone receptor we have described on integrin αvβ3. The thyroid hormone isoforms also caused serine phosphorylation of ER in NCI-H522 and NCI-H510A cells. The ER antagonist, ICI 182,780 (fulvestrant) inhibited stimulation by T4 and T3 of ER phosphorylation, of PCNA accumulation and of radiolabeled thymidine incorporation by the cells. These results are consistent with existence of crosstalk between the plasma membrane receptor for iodothyronines and ER in these lung cancer cells. We conclude that endogenous T4 is a growth factor for ER-containing lung cancer cells and this hormonal action is subject to inhibition by tetrac and by fulvestrant. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C146.