Adhesion, migration, transcriptional, interferon-inducible, and other signaling molecules newly implicated in cancer susceptibility and resistance of JB6 cells by cDNA microarray analyses.

Relative expression levels of 9500 genes were determined by cDNA microarray analyses in mouse skin JB6 cells susceptible (P+) and resistant (P-) to 12-O-tetradecanoyl phorbol-13 acetate (TPA)-induced neoplastic transformation. Seventy-four genes in 6 functional classes were differentially expressed: (I) extracellular matrix (ECM) and basement membrane (BM) proteins (20 genes). P+ cells express higher levels than P- cells of several collagens and proteases, and lower levels of protease inhibitors. Multiple genes encoding adhesion molecules are expressed preferentially in P- cells, including six genes implicated in axon guidance and adhesion. (II) Cytoskeletal proteins (13 genes). These include actin isoforms and regulatory proteins, almost all preferentially expressed in P- cells. (III) Signal transduction proteins (12 genes). Among these are Ras-GTPase activating protein (Ras-GAP), the deleted in oral cancer-1 and SLIT2 tumor suppressors, and connexin 43 (Cx43) gap junctional protein, all expressed preferentially in P- cells. (IV) Interferon-inducible proteins (3 genes). These include interferon-inducible protein (IFI)-16, an Sp1 transcriptional regulator expressed preferentially in P- cells. (V) Other transcription factors (4 genes). Paired related homeobox gene 2 (Prx2)/S8 homeobox, and retinoic acid (RA)-regulated nur77 and cellular retinoic acid-binding protein II (CRABPII) transcription factors are expressed preferentially in P- cells. The RIN-ZF Sp-transcriptional suppressor exhibits preferential P+ expression. (VI) Genes of unknown functions (22 sequences). Numerous mesenchymal markers are expressed in both cell types. Data for multiple genes were confirmed by real-time PCR. Overall, 26 genes were newly implicated in cancer. Detailed analyses of the functions of the genes and their interrelationships provided converging evidence for their possible roles in implementing genetic programs mediating cancer susceptibility and resistance. These results, in conjunction with cell wounding and phalloidin staining data, indicated that concerted genetic programs were implemented that were conducive to cell adhesion and tumor suppression in P- cells and that favored matrix turnover, cell motility, and abrogation of tumor suppression in P+ cells. Such genetic programs may in part be orchestrated by Sp-, RA-, and Hox-transcriptional regulatory pathways implicated in this study.