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Cellular dichotomy between anchorage‐independent growth responses to bFGF and TPA reflects molecular switch in commitment to carcinogenesis
Author(s) -
Waters Katrina M.,
Tan Ruimin,
Opresko Lee K.,
Quesenberry Ryan D.,
Bandyopadhyay Somnath,
Chrisler William B.,
Weber Thomas J.
Publication year - 2009
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20558
Subject(s) - biology , carcinogenesis , phenotype , ectopic expression , transcription factor , gene expression , microbiology and biotechnology , basic fibroblast growth factor , gene , growth factor , cancer research , genetics , receptor
We have investigated gene expression patterns underlying reversible and irreversible anchorage‐independent growth (AIG) phenotypes to identify more sensitive markers of cell transformation for studies directed at interrogating carcinogenesis responses. In JB6 mouse epidermal cells, basic fibroblast growth factor (bFGF) induces an unusually efficient and reversible AIG response, relative to 12‐ O ‐tetradecanoyl phorbol‐13‐acetate (TPA)‐induced AIG which is irreversible. The reversible and irreversible AIG phenotypes are characterized by largely nonoverlapping global gene expression profiles. However, a subset of differentially expressed genes were identified as common to reversible and irreversible AIG phenotypes, including genes regulated in a reciprocal fashion. Hepatic leukemia factor (HLF) and D‐site albumin promoter‐binding protein (DBP) were increased in both bFGF and TPA soft agar colonies and selected for functional validation. Ectopic expression of human HLF and DBP in JB6 cells resulted in a marked increase in TPA‐ and bFGF‐regulated AIG responses. HLF and DBP expression were increased in soft agar colonies arising from JB6 cells exposed to gamma radiation and in a human basal cell carcinoma tumor tissue, relative to paired nontumor tissue. Subsequent biological network analysis suggests that many of the differentially expressed genes that are common to bFGF‐ and TPA‐dependent AIG are regulated by c‐Myc, SP‐1, and HNF‐4 transcription factors. Collectively, we have identified a potential molecular switch that mediates the transition from reversible to irreversible AIG. © 2009 Wiley‐Liss, Inc.