GRO-alpha: a potential marker for cancer and aging silenced by RNA interference.
Age-regulated genes may serve as markers of aging, enabling assessment of physiological aging independent of chronological age. One gene with transcripts that increase in abundance with age in human organs, inter alia in epithelial skin cells, is the chemokine growth-regulated protein alpha (GRO-alpha). When chemokines, such as GRO-alpha, become disregulated so that they are chronically expressed, tissue damage, angiogenesis, and tumorigenesis can follow. To consider the role of GRO-alpha as a potential marker for aging and cancer, we compared the transient knockdown of GRO-alpha by RNA interference in the human sebaceous gland cell line SZ95, which behaves like normal human sebocytes, and in the melanoma cell line A375, which originates from a primary human tumor. The reduced GRO-alpha RNA expression, of about 75% in SZ95 sebocytes and 58% in A375 melanoma cells, has functional consequences in normal aged cells and in cancer cells. Silencing of the proangiogenic chemokine GRO-alpha is proportionally correlated with interleukin-6 (IL-6), IL-8 and vascular endothelial growth factor secretion in both cell types. Thus, GRO-alpha may be a novel diagnostic marker for age-related pathology, including cancer.
Fimmel
Sabine
S
Universitätsklinikum Charité CBF, Institut für Klinische Pharmakologie und Toxikologie, Garystr. 5, Berlin, Germany. sabine.fimmel@charite.de
Devermann
Lena
L
Herrmann
Anke
A
Zouboulis
Christos
C
D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000235:genetics; D054360:Chemokine CXCL1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012627:Sebaceous Glands / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D016207:Cytokines; D034741:RNA, Small Interfering