Expression of the retinoblastoma (RB) tumor suppressor gene inhibits tumor cell invasion in vitro.
To determine if replacement of the retinoblastoma (RB) tumor suppressor gene could inhibit invasion of RB-defective tumor cells, the capacity of tumor cells to migrate or invade was quantitated by the Boyden chamber assay. The studies were done in a diverse group of stable RB-reconstituted human tumor cell lines, including those derived from the osteosarcoma and carcinomas of the lung, breast and bladder. The expression of the exogenous wild-type RB protein in these tumor cell lines was driven by either a constitutively active promoter or an inducible promoter. It was found that significantly more tumor cells from the parental RB-defective cell lines and the RB revertants than from the RB-reconstituted RB+ cell lines penetrated through the Matrigel (P<0.001, two-tailed t-test), although both RB+ and RB- cells migrated at approximately the same rate on uncoated polycarbonate filters in the Boyden chambers. Of note, the inhibition of invasiveness of various RB-defective tumor cells by RB replacement was apparently well correlated with suppression of their tumorigenicity in vivo. In contrast, although either functional RB or p53 re-expression effectively suppressed tumor formation in nude mice of the RB-/p53null osteosarcoma cell line, Saos-2, replacement of the wild-type p53 gene had much less impact on their invasiveness as compared to the RB gene. These studies provided an insight into the broader biological basis of the RB-mediated tumor suppression in RB-defective tumor cells.
Li
J
J
Department of Molecular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Hu
S X
SX
Perng
G S
GS
Zhou
Y
Y
Xu
K
K
Zhang
C
C
Seigne
J
J
Benedict
W F
WF
Xu
H J
HJ
D000818:Animals; D002465:Cell Movement; D002633:Chemotaxis; D003094:Collagen; D015194:Diffusion Chambers, Culture; D004338:Drug Combinations; D016161:Genes, Retinoblastoma / Q000235:genetics / Q000502:physiology*; D016158:Genes, p53 / Q000502:physiology; D005822:Genetic Vectors; D006801:Humans; D007797:Laminin; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011509:Proteoglycans; D016160:Retinoblastoma Protein / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D007797:Laminin; D009363:Neoplasm Proteins; D011509:Proteoglycans; D016160:Retinoblastoma Protein; C059485:matrigel; D003094:Collagen