The differential expression of hCNT1 and hENT1 i n breast cancer and the possible impact on breast cancer therapy.
hCNT1 and hENT1, two members of the human nucleoside transporter families, expression levels were investigated, in normal and in breast tumour tissues, together with effects of gemcitabine cytotoxicity and in vivo tumour growth in MDA-MB-231 cells. hCNT1 and hENT1 levels were lower in tumour samples than in normal background tissue (p < 0.48). hENT1 levels decreased significantly with patient prognosis (disease free versus died from breast cancer, p = 0.047) although hCNT1 expression did not (disease free versus died from breast cancer, p = 0.97). Immunohistochemical staining of hCNT1 and hENT1 was stronger in normal than tumour tissue. hCNT1 knockdown caused MDA-MB-231 cells to be less sensitive to Gemcitabine compared with wild type and control plasmid cells (25% killed vs 88% and 90%). MDA MB-231 deltahENT1 (p = 0.139) and MDA MB-231deltahCNT1 (p = 0.033) tumours showed reduced growth compared with wild type, [71.99 +/- 39.81 mm3 MDA MB-231WT, 40.58 +/- 20.61 mm3 MDA MB-231 deltahCNT1 tumours, 51.58 +/- 49.29 mm3 MDA MB-231deltahENT1, 79.55 +/- 63.08 mm3 PEF and 57.92 +/- 21.67 mm3 GFP controls]. This study shows variability in hCNT1 and hENT1 expression in tumour and normal human breast tissue with different expression patterns related to patient prognosis and clinical outcome. The level of expression of CNT1 was closely linked to the cell's responsiveness to chemotherapeutic treatments.
Lane
Jane
J
School of Medicine, Cardiff University, Cardiff, Wales, United Kingdom.
Martin
Tracey A
TA
McGuigan
Christopher
C
Mason
Malcolm D
MD
Jiang
Wen G
WG
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D033721:Equilibrative Nucleoside Transporter 1 / Q000032:analysis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D026901:Membrane Transport Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D000093542:Gemcitabine
D033721:Equilibrative Nucleoside Transporter 1; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; C438649:SLC29A1 protein, human; C065171:cif nucleoside transporter; D003841:Deoxycytidine; D000093542:Gemcitabine