Differential gene expression and clonal selection during cellular transformation induced by adhesion deprivation.
BACKGROUND
Anchorage independent growth is an important hallmark of oncogenic transformation. Previous studies have shown that when adhesion dependent fibroblasts were prevented from adhering to a substrate they underwent anoikis. In the present study we have demonstrated how anoikis resistant cells gain the transformation related properties with sequential selection of genes. We have proposed this process as a model system for selection of transformed cells from normal cells.


RESULTS
This report demonstrates that some fibroblasts can survive during late stages of anoikis, at which time they exhibit transformation-associated properties such as in vitro colony formation in soft agar and in vivo subcutaneous tumour formation in nude mice. Cytogenetic characterisation of these cells revealed that they contained a t (2; 2) derivative chromosome and they have a selective survival advantage in non adherent conditions. Gene expression profile indicated that these cells over expressed genes related to hypoxia, glycolysis and tumor suppression/metastasis which could be helpful in their retaining a transformed phenotype.


CONCLUSIONS
Our results reveal some new links between anoikis and cell transformation and they provide a reproducible model system which can potentially be useful to study multistage cancer and to identify new targets for drug development.
Department of Biochemistry, Acharya Nagarjuna University, Guntur 522510,India.
Rajeswari
R
Jinka
Renu
R
Kapoor
Sivapriya
S
Pavuluri
Avinash T
AT
Raj
Mahesh J
MJ
Kumar
Lakshmi
L
Rao
Gopal
G
Pande
D000818:Animals; D002448:Cell Adhesion; D002461:Cell Line, Transformed; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D020869:Gene Expression Profiling; D006019:Glycolysis / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007621:Karyotyping; D051379:Mice; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D006023:Glycoproteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C051795:teleocalcin