PHTS, a novel putative tumor suppressor, is involved in the transformation reversion of HeLaHF cells independently of the p53 pathway.
HeLaHF is a non-transformed revertant of HeLa cells, likely resulting from the activation of a putative tumor suppressor(s). p53 protein was stabilized in this revertant and reactivated for certain transactivation functions. Although p53 stabilization has not conclusively been linked to the reversion, it is clear that the genes in p53 pathway are involved. The present study confirms the direct role of p53 in HeLaHF reversion by demonstrating that RNAi-mediated p53 silencing partially restores anchorage-independent growth potential of the revertant through the suppression of anoikis. In addition, we identified a novel gene, named PHTS, with putative tumor suppressor properties, and showed that this gene is also involved in HeLaHF reversion independently of the p53 pathway. Expression profiling revealed that PHTS is one of the genes that is up-regulated in HeLaHF but not in HeLa. It encodes a putative protein with CD59-like domains. RNAi-mediated PHTS silencing resulted in the partial restoration of transformation (anchorage-independent growth) in HeLaHF cells, similar to that of p53 gene silencing, implying its tumor suppressor effect. However, the observed increased transformation potential by PHTS silencing appears to be due to an increased anchorage-independent proliferation rate rather than suppression of anoikis, unlike the effect of p53 silencing. p53 silencing did not affect PHTS gene expression, and vice versa, suggesting PHTS may function in a new and p53-independent tumor suppressor pathway. Furthermore, over-expression of PHTS in different cancer cell lines, in addition to HeLa, reduces cell growth likely via induced apoptosis, confirming the broad PHTS tumor suppressor properties.
Yu
De-Hua
DH
Immusol, Inc. 10790 Roselle Street, San Diego, CA 92121, USA.
Fan
Wufang
W
Liu
Guohong
G
Nguy
Vivian
V
Chatterton
Jon E
JE
Long
Shilong
S
Ke
Ning
N
Meyhack
Bernd
B
Bruengger
Adrian
A
Brachat
Arndt
A
Wong-Staal
Flossie
F
Li
Qi-Xiang
QX
D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010641:Phenotype; D034622:RNA Interference / Q000502:physiology; D014170:Transformation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D058851:GPI-Linked Proteins; C510169:LYPD1 protein, human; D008565:Membrane Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins