Role of Pax2 in apoptosis resistance and proinvasive phenotype of Kaposi's sarcoma cells.
In this study, we found that Kaposi's sarcoma cells but not human microvascular endothelial cells expressed PAX2, a gene coding for a transcription factor involved both in organogenesis and tumorigenesis. Moreover, Pax2 was frequently expressed, on spindle-shaped cells, in Kaposi's sarcoma lesions. We cloned PAX2 from Kaposi's sarcoma cells and obtained antisense and sense DNA. Transfection of Kaposi's sarcoma cells with antisense DNA, which suppressed Pax2 protein expression, reduced cell growth and survival and enhanced the sensitivity of Kaposi's sarcoma cells to apoptosis induced by serum deprivation or vincristine treatment. In addition, antisense transfection inhibited the cell motility, the invasion of Matrigel, and the spindle shape morphology, which are characteristics of Kaposi's sarcoma cells. Moreover, the alphavbeta3 integrin, known to be involved in tumor invasion, was down-regulated. To evaluate the possible role of Pax2 expression in the endothelial origin of Kaposi's sarcoma cells, human microvascular endothelial cells were transfected with sense DNA. Endothelial cells transfected with sense PAX2 acquired spindle shape morphology, showed enhanced motility and Matrigel invasion, and displayed an enhanced expression of alphavbeta3 integrin. In conclusion, the expression of Pax2 by Kaposi's sarcoma cells correlated with an enhanced resistance against apoptotic signals and with the proinvasive phenotype. Moreover, PAX2-transfected endothelial cells acquired a phenotype resembling that of Kaposi's lesional cells, suggesting a role of this embryonic gene in tumorigenesis.
Buttiglieri
Stefano
S
Cattedra di Nefrologia, Dipartimento di Medicina Interna and Centro Ricerca Medicina Sperimentale, Università di Torino, Torino 10126, Italy.
Deregibus
Maria Chiara
MC
Bravo
Stefania
S
Cassoni
Paola
P
Chiarle
Roberto
R
Bussolati
Benedetta
B
Camussi
Giovanni
G
D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002453:Cell Cycle; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D051762:PAX2 Transcription Factor; D010641:Phenotype; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D011994:Recombinant Proteins; D014157:Transcription Factors