Effect of Gene 33/Mig6/ERRFI1 on hexavalent chromium-induced transformation of human bronchial epithelial cells depends on the length of exposure

Abstract

Hexavalent chromium (Cr(VI)) compounds are environmental and occupational lung carcinogens. The present study followed the chronic effect of Cr(VI) on the neoplastic transformation of BEAS-2B lung bronchial epithelial cells with or without deletion of Gene 33 (Mig6, EFFRI1), a multifunctional adaptor protein. We find that Gene 33-deleted cells exhibit increased anchorage-independent growth compared to control cells after transformed by 8-week but not 24-week Cr(VI) exposure. Gene 33-deleted cells show a higher level of cell proliferation and are more resistant to acute Cr(VI) toxicity compared to control cells after transformed by 8-week but not 24-week Cr(VI) exposure, despite that 24-week-transformed cells have increased resistance to acute Cr(VI) toxicity. However, Gene 33-deleted cells show increased migration after transformed by both 8-week and 24-week Cr(VI) exposures. Furthermore, only cells transformed by 24 weeks of Cr(VI) exposure can form subcutaneous tumors in nude mice. Although no significant difference in the size of tumors formed by the two cell types, there is a marked difference in the histological manifestation and more MMP3 expression in tumors from Gene 33-deleted cells. Our results demonstrate progressive neoplastic transformation of BEAS-2B cells and the adaptation of these cells to Gene 33 deletion during chronic exposure to Cr(VI).

Keywords:

• Gene 33/Mig6/ERRFI1
• transformation
• tumor
• lung
• chromium

Authors’ contributions

CL, DE, SP, RL, JL, MH, and MR performed the experiments; HI and JLP critically reviewed the manuscript; DX designed the study and drafted the manuscript.

Disclosure statement

The authors declare that they have no conflicts of interest with the contents of this article.

Data availability statement

Amplicon sequencing data supporting this study are openly available in Mendeley Data at DOI: 10.17632/7k88p4k54b.2. Other data are available upon request.

Additional information

Funding

This work was supported in part by a Touro/NYMC bridge grant (DX) and Empire Clinical Research Investigator Program award (DX and JP).