Deletion of A-antigen in a human cancer cell line is associated with reduced promoter activity of CBF/NF-Y binding region, and ... View Full Text


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Article Info

DATE

1999-10

AUTHORS

Sadahiko Iwamoto, Donald A. Withers, Kazuko Handa, Sen-itiroh Hakomori

ABSTRACT

Employing blood group A- and A+ clones derived from the same parental colonic cancer cell lines, we studied the molecular mechanism of deletion/reduction vs. continuous expression of A antigen in A tumors, a crucial determinant of human tumor malignancy. A- transferase mRNA level in one of the A- clones (A- SW480) was undetectable, while that in A+ SW480 was strongly detectable by semiquantitative RT-PCR. Relatively lower (approximately 1/3) transcript level was detectable in another A- clone (A- HT29) in comparison to A+ HT29 by the same RT-PCR procedure, although none of these tumor cell lines showed detectable level of A transcript by Northern blotting or RNase protection methods. Therefore, subsequent studies were performed employing A- vs. A+ SW480 clones. Deletion of A transcript in A- cells was not due to gene deletion, since Southern blot analysis showed equal presence of genomic DNA regardless of A- vs. A+ (SW480 or HT29) or B+ (KATOIII) tumor cells. Two transcriptional control mechanisms leading to differences of A expression in SW480 cells are indicated. i. Luciferase assay in A- and A+ SW480 cells showed that promoter activities of segments of 5' flanking sequence of ABO gene reflected transcript levels in these cell lines. The enhancing activity of a 43 bp tandem repeat unit located between -3899 to -3618 was reduced in A- compared to A+ cells. ii. Distinct differences in the pattern of CpG dinucleotide methylation were found in A- vs. A+ cells. Therefore, the methylation process of A promoter DNA may be another important factor controlling A activity in SW480 tumor cells. Since proliferation and motility of tumor cells are associated closely with A expression, transcription control mechanism for expression of A transferase as described above may be of crucial importance in defining human tumor malignancy. More... »

PAGES

659-666

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1023/a:1007085202379

DOI

http://dx.doi.org/10.1023/a:1007085202379

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1029037365

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10972144


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