cyclin-d1 and Cystadenocarcinoma--Papillary

The expression status of p27 and cyclin D1 was examined in 21 uterine papillary serous carcinoma (UPSC) specimens to determine the role of these genes in the development of this disease. The status of p53, p16, Rb, and K-ras was also determined in these tissues so that a marker profile for UPSC could be compared with the published marker profile for other forms of endometrial and ovarian cancer.. Immunohistochemistry was performed on 21 UPSC tissue sections to determine the expression status of p27, cyclin D1, p53, p16, and Rb. K-ras mutations were identified by restriction fragment length polymorphism analysis of DNA isolated from the UPSC sections.. All specimens displayed at least one molecular abnormality. A high incidence of p27 alterations were observed, with reduced p27 expression measured in 16 of 21 (76%) tumors, followed by p53 alterations observed in 13 of 21 (62%) tumors. The p27 abnormalities occur at an early stage of the disease, with 63% (5/8) of Stage I cases displaying reduced p27 expression. Cyclin D1 overexpression was observed in 4 of 21 (19%) specimens, whereas p16, Rb, and K-ras abnormalities were each observed in 2 of 21 specimens (10%). Both K-ras mutations were at codon 12. The p16 and Rb abnormalities coexisted in the same specimens.. UPSC tumors display a high incidence of p27 abnormalities, suggesting that p27 abnormalities play an important role in the development of this disease. Our results also indicate that cyclin D1 overexpression is involved in the development of a small number of UPSC cases. A comparison of our results with reports by other authors suggests that UPSC shares molecular marker alterations with both ovarian cancer and endometrioid adenocarcinoma.

Topics: Adult; Cell Cycle Proteins; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p27; Cystadenocarcinoma, Papillary; DNA Mutational Analysis; Female; Genes, ras; Humans; Microtubule-Associated Proteins; Point Mutation; Tumor Suppressor Protein p53; Tumor Suppressor Proteins; Uterine Neoplasms

Dysregulation of cyclin expression has been reported for several human malignancies, including breast cancer. To further investigate the role of cyclin genes in mammary tumorigenesis we analyzed the expression of cyclins D1, E and A and other cell cycle-related proteins in a series of nine N-methyl-N-nitrosourea-induced primary rat mammary tumors. Western blot analysis revealed a 10- to 15-fold increase in the level of cyclin D1 protein in most (7/9) of the tumors, when compared with normal rat mammary gland. The two tumors that did not show this increase also displayed negligible levels of the retinoblastoma protein. A moderate increase, 1.5- to 2-fold, in the level of cyclin E was observed in four tumors and three tumors displayed abnormal low molecular weight cyclin E-related proteins. None of the tumors showed amplification of the cyclin D1 or E genes when studied by Southern blot analysis. All nine tumors showed a 2- to 6-fold increase in the level of cyclin A protein. Most of the tumors also displayed a marked increase in levels of the CDK2 and CDK4 proteins. These changes did not appear to be simply a consequence of increased cell proliferation, as assessed by proliferating cell nuclear antigen analysis. Thus, aberrant expression of cyclins and other cyclin-related genes occurs frequently in mammary tumorigenesis in both rodents and humans.

Topics: Animals; Carcinogens; CDC2-CDC28 Kinases; Cell Cycle; Cell Division; Cyclin D1; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases; Cyclins; Cystadenocarcinoma, Papillary; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Mammary Neoplasms, Experimental; Methylnitrosourea; Oncogene Proteins; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Rats; Rats, Sprague-Dawley