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The PRAD‐1/cyclin D1 oncogene product accumulates aberrantly in a subset of colorectal carcinomas
Author(s) -
Bartkova Jirina,
Lukas Jiri,
Strauss Michael,
Bartek Jiri
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580420
Subject(s) - cyclin d1 , cancer research , oncogene , cell cycle , colorectal cancer , immunostaining , biology , cyclin , retinoblastoma protein , immunohistochemistry , pathology , cancer , cyclin d , medicine , immunology , genetics
Abstract The PRAD‐l/cyclin Dl proto‐oncogene is localized on chromosome 11 q 13 and it is overexpressed in several tumour types as a consequence of gene amplification or chromosomal rearrangements. In this study, the abundance and patterns of cyclin Dl protein expression in normal/non‐involved colon (n = 44), primary (n = 48) and metastatic (n = 9) colorectal carcinomas, and in a series of 4 colon cancer cell lines were investigated by immunochemical methods using the DCS‐6 monoclonal antibody specific for cyclin Dl. While examination of all normal colorectal tissue samples and 56% of the primary tumours revealed only weak to undetectable immunostaining signals, 23% of the primary carcinomas showed moderate and 21% showed strong aberrant accumulation of this cell‐cycle regulatory oncoprotein. The immunohistochemical patterns in the secondary lesions were concordant with the matched primary tumours in all cases. The staining was nuclear both in the clinical specimens and in the colon cancer cell lines, in which the antibody‐mediated knock‐out experiments demonstrated a positive regulatory role of the cyclin Dl protein whose function was required for progression through the G1 phase of the cell cycle. These results indicate that the PRAD‐l/cyclin Dl protooncogene may be deregulated in a significant subset of colorectal tumours, and warrant further analyses of such aberrations of the cyclin Dl/retinoblastoma protein pathway to elucidate its potential involvement in the multistep pathogenesis of human colorectal cancer.