KiSS-1 expression in human breast cancer.
The KiSS-1 gene encodes a 145 amino acid residue peptide that is further processed to a final peptide, metastin, a ligand to a G-coupled orphan receptor (OT7T175/AXOR12). KiSS-1 has been identified as a putative human metastasis suppressor gene in melanomas and in breast cancer cell lines. This study aimed to determine the expression and distribution of KiSS-1 and its receptor in human breast cancer tissues and to identify a possible link between expression levels and patient prognosis. Frozen sections from breast cancer primary tumours (matched tumour 124 and background 33) were immuno-stained with KiSS-1 antibody. RNA was reverse transcribed and analyzed by Q-PCR (standardized using beta-actin, and normalized with cytokeratin-19 levels). Levels of expression of KiSS-1 were higher in tumour compared to background tissues (3,124+/-1,262 vs 2,397+/-1,181) and significantly increased in node positive tumours compared to node negative (3,637+/-1,719 vs 2,653+/-1,994, P = 0.02). KiSS-1 expression was also increased with increasing grade and TNM status. There were no such trends with the KiSS-1 receptor. Expression of KiSS-1 was higher in patients who had died from breast cancer than those who had remained healthy (4,631+/-3,024 vs 2,280+/-1,403) whereas expression of the receptor was reduced (480+/-162 vs 195+/-134). Immunohistochemical staining showed increased expression of KiSS-1 in tumour sections. Insertion of the KiSS-1 gene into the human breast cancer cell line MDA-MB-231, resulted in cells that were significantly more motile and invasive in behaviour, with reduced adhesion to matrix, using respective assays. In conclusion, KiSS-1 expression is increased in human breast cancer, particularly in patients with aggressive tumours and with mortality. Over-expression of KiSS-1 in breast cancer cells result in more aggressive phenotype. Together, it suggests that KiSS-1 plays a role beyond the initial metastasis repressor in this cancer type.
Martin
Tracey A
TA
Metastasis & Angiogenesis Research Group, University Department of Surgery, Wales College of Medicine, Cardiff University, Cardiff, UK. Martinta1@cf.ac.uk
Watkins
Gareth
G
Jiang
Wen G
WG
D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D059648:Kisspeptins; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D044088:Receptors, Galanin / Q000032:analysis / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D014162:Transfection; D025521:Tumor Suppressor Proteins
C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D011506:Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D044088:Receptors, Galanin; D000074502:Receptors, Kisspeptin-1; D025521:Tumor Suppressor Proteins