Abstract
Previous work in our laboratory using functional assays for tumorigenicity identified a tumor suppressor element on human chromosome 11q for the cutaneous squamous cell carcinoma cell line A388.6TG.c2. In this report, we screened a variety of agents for differential effects on A388.6TG.c2 compared to a growth-suppressed chromosome 11 microcell hybrid of A388.6TG.c2. One of the agents, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3; calcitriol), exerted a growth-altering effect on A388.6TG.c2, which formed rounded cell clusters across the surface of the raft by Day 6 of treatment. In contrast, full-length chromosome 11 hybrids of A388.6TG.c2, as well as two other squamous cell carcinoma cell lines (FaDu and A431), when treated with 1,25(OH)2D3, failed to demonstrate this cell-clumping phenotype. To pursue the hypothesis that the growth suppressor element is involved in altering the response to 1,25(OH)2D3, we tested microcell hybrids carrying t(X;11) chromosomes lacking large portions of 11q. Although these hybrids, like the parent A388.6TG.c2 cells, demonstrated extensive growth in organotypic cultures, they failed to form cell clusters with 1,25(OH)2D3 treatment. These results suggest that the chromosome 11 element that alters the response to 1,25(OH)2D3 is distinct from the growth-suppressing element. An examination of differentiation marker expression revealed identical patterns of basal and suprabasal markers for A388.6TG.c2 and for a chromosome 11 hybrid with or without treatment with 1,25(OH)2D3. Finally, characterization of candidate tumor suppressor gene PPP2R1B, which encodes for a subunit of protein phosphatase 2A (PP2A), showed seemingly insignificant alterations by cDNA sequence analysis. Collectively, the data suggest that human chromosome 11 contains two different tumor suppressor elements that may account for the two areas of loss of heterozygosity observed on the long arm of this chromosome.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
