Delta-6-desaturase (D6D) activity is deficient in MCF-7 and other cancer cell lines, but it is not explained by gene mutations. This deficient activity was not ameliorated by induction of the gene; therefore, we hypothesized that some of the induced transcript variants () may play a negative regulatory role. is the reference , coding for full-length D6D isoform 1 (D6D-iso1), and alternative transcriptional start sites result in and variants encoding D6D-iso2 and D6D-iso3 isoforms, respectively, which lack the catalytically critical N-terminal domain. In MCF-7 cells, and were expressed at significantly higher levels than . Overexpression of in HEK293 cells confirmed that D6D-iso2 is non-functional, and ... More
Delta-6-desaturase (D6D) activity is deficient in MCF-7 and other cancer cell lines, but it is not explained by gene mutations. This deficient activity was not ameliorated by induction of the gene; therefore, we hypothesized that some of the induced transcript variants () may play a negative regulatory role. is the reference , coding for full-length D6D isoform 1 (D6D-iso1), and alternative transcriptional start sites result in and variants encoding D6D-iso2 and D6D-iso3 isoforms, respectively, which lack the catalytically critical N-terminal domain. In MCF-7 cells, and were expressed at significantly higher levels than . Overexpression of in HEK293 cells confirmed that D6D-iso2 is non-functional, and co-transfection demonstrated a dominant-negative role for D6D-iso2 in D6D-iso1 activity regulation. was expressed at higher levels than in HeLa, MDA-MB-435, MCF-10 A, and HT-29 cells, but at lower levels in A549, MDA-MB-231, and LNCaP cells. Overexpression studies indicated roles for variants in proliferation and apoptosis regulation, which were also cell-line specific. Increased expression provides a new mechanism to help explain deficient D6D activity in MCF-7 and other cancer cell lines, but it is not a hallmark of malignant cells.
