Loss of c-KIT expression in thyroid cancer cells

PLoS One. 2017 Mar 16;12(3):e0173913. doi: 10.1371/journal.pone.0173913. eCollection 2017.

Abstract

Papillary thyroid carcinoma is the most frequent histologic type of thyroid tumor. Few studies investigated the role of c-KIT expression in thyroid tumors, suggesting a role for this receptor and its ligand in differentiation and growth control of thyroid epithelium and a receptor loss following malignant transformation. We investigated and correlated c-KIT expression levels and two known markers of thyrocytes differentiation, PAX8 and TTF-1, in malignant and benign cytological thyroid samples. Moreover, we performed functional studies on human papillary thyroid carcinoma cell line to associated c-KIT expression to thyrocytes differentiation and tumor proliferation. c-KIT and PAX8 expression resulted higher in benign samples compared to the malignant ones, and the expression levels of these two genes were significantly correlated to each other. We also observed that c-KIT overexpression led to an increase of PAX8 expression level together with a decrease of proliferation. Furthermore, c-KIT overexpressing cells showed a regression of typical morphological features of malignancy. Taken together these results suggest that c-KIT could be involved in the differentiation of thyroid cells and in tumor progression.

MeSH terms

  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • Carcinoma, Papillary
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Nuclear Proteins / metabolism
  • PAX8 Transcription Factor / metabolism
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology
  • Thyroid Nuclear Factor 1
  • Transcription Factors / metabolism

Substances

  • NKX2-1 protein, human
  • Nuclear Proteins
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • Proto-Oncogene Proteins c-kit

Grant support

The authors received no specific funding for this work.