Expression of human delta-6-desaturase is associated with aggressiveness of human breast cancer.
Highly unsaturated fatty acids (HUFAs) are cyto-toxic to cancer cells and generated in the body by desaturation from essential fatty acids, primarily involving delta-6-desaturase. This study, for the first time, examined the level of expression of human delta-6-desaturase as well as delta-4-desaturase in human breast cancer. Breast tumours (n=102) which comprised of 88 ductal and 14 lobular carcinomas, as well as normal breast tissues (n=31), together with breast cancer cell lines were analysed for the level of expression of delta-6- and delta-4-desaturases using RT-PCR and quantitative PCR. A lower level of delta-6-desaturase was seen in breast tumour compared with normal tissues. Tumours from patients who had a poor prognostic index and from those who died of breast cancer had the lowest level of delta-6-desaturase (median follow-up 72 months). In addition, TNM3 and TNM4 tumours had significantly lower level of delta-6-desaturase than TNM1 tumours. Interestingly, ductal tumours displayed significantly higher level of the enzyme than lobular tumours. In contrast, a stepwise increase of delta-4-desaturase was seen in tumour from patients with poor prognosis. It is concluded that aggressive breast tumours have a reduced level of delta-6-desaturase. This aberrant expression has clinical bearings to the outcome in patients with breast cancer.
Lane
Jane
J
Metastasis Research Group, University Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Mansel
Robert E
RE
Jiang
Wen G
WG
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000201:enzymology* / Q000473:pathology*; D044943:Fatty Acid Desaturases / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050602:Linoleoyl-CoA Desaturase; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012016:Reference Values
D044943:Fatty Acid Desaturases; D050602:Linoleoyl-CoA Desaturase; C434953:delta-4 fatty acid desaturase