mRNA and protein expression of fetal insulin receptor in breast cancer cell lines and tissues.

BACKGROUND

The insulin receptor (IR) is expressed in breast cancer cells and plays a role in regulating tumor biology. There are two IR isoforms generated from the same gene. Alternate splicing with exclusion or inclusion of exon 11 accounts for the two isoforms. The exon 11 excluded isoform (IR-A) is expressed during fetal development while the full-length adult IR (IR-B) is the primary form expressed during adult life. This splice variant results in a 12 amino acid variation in peptide sequence. Breast cancer cells overexpress IR-A with an increased IR-A: IR-B ratio. Most of these data were obtained by examining mRNA expressions.

METHODS

In this work, we examined over 40 breast cancer cell lines and patient tumor samples for mRNA expression of the IR isoforms. Further we used mass spectrometry to evaluate IR-A protein expression.

RESULTS

Most breast cancer cell lines and tissues overexpress IR-A compared to IR-B. Mass spectrometry analysis demonstrated IR-A protein expression in the Du4475 cell line which has a high level of IR-A mRNA expression.

CONCLUSION

IR-A mRNA is frequently expressed in breast cancer cells. To our knowledge, this is the first demonstration of IR-A protein expression. Thus, IR-A mRNA and protein expression demonstrate a potential role for this insulin receptor isoform in breast cancer biology.