Intrinsic gene changes determine the successful establishment of stable renal cancer cell lines from tumor tissue

Int J Cancer. 2017 Jun 1;140(11):2526-2534. doi: 10.1002/ijc.30674. Epub 2017 Mar 16.

Abstract

Human tumor cell lines, especially those with complete data and follow-up, are important tools in tumor biological studies. Clear cell renal cell cancer (ccRCC) is not sensitive to radiotherapy or chemotherapy, and treatment of patients with distant metastasis relies on targeted therapy. Here, we report the establishment of seven new ccRCC stable cell lines that were continuously cultured for more than 20 generations among 81 cases of renal cell cancer. Moreover, gene expression and methylation in the established cell lines, in those that had a finite in vitro life span of less than 10 generations, and in cells that originated from the same culture at different generations were profiled using microarrays. Genes including SLC34A2, SEPP1, SULT1C4 and others were differentially expressed in established cell lines and finite cell lines, and changes in their expression might be caused by methylation or demethylation. The expression level of SLC34A2 was related not only to the life span in vitro culture but also to tumor size. Additionally, six of the seven new ccRCC cell lines had VHL deletions or termination mutations. So in addition to the establishment of seven new ccRCC cell lines with complete clinical data, we conclude that genes such as SLC34A2 and VHL play key roles in the continuous in vitro growth and development of ccRCC.

Keywords: SLC34A2; VHL; clear cell renal cell carcinoma; stable cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology*
  • Male
  • Methylation
  • Middle Aged
  • Mutation / genetics
  • Sodium-Phosphate Cotransporter Proteins, Type IIb / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics

Substances

  • SLC34A2 protein, human
  • Sodium-Phosphate Cotransporter Proteins, Type IIb
  • Von Hippel-Lindau Tumor Suppressor Protein