Expression of the Components of the Cip/Kip Family in Malignant Lymphoma of the Thyroid

Abstract

Objective: For evaluating the characteristics of human neoplasms, investigation of regulators of cell cycle progression is important. We studied three components of the Cip/Kip family, p57, p27 and p21, in malignant lymphomas of the thyroid. Methods: We immunohistochemically investigated the expression of the three proteins for 49 cases of thyroid lymphomas, as well as 10 cases of chronic thyroiditis. Results: In infiltrating lymphocytes in chronic thyroiditis, p57 and p27 were diffusely expressed, whereas p21 immunoreactivity was only occasionally observed. In lymphoma, decreased expression of p57 (less than 50% of lymphoma cells were positive) was observed in 24 cases (49.0%). p57 expression was inversely linked to the MIB-1 labeling index, grade of malignancy and aberrant p53 expression. Decreased expression of p27 was observed in 25 cases (51.0%), which was also related to the MIB-1 labeling index and aberrant p53 expression. On the other hand, p21 expression was occasional, and when the cut-off value was set at 3%, 38 cases (77.6%) were regarded as negative. P21 expression was not linked to any clinicopathological parameters. Conclusion: These findings suggest that, among the 3 components of the Cip/Kip family, p57 and p27 play a role in negatively regulating the cell proliferation of thyroid lymphoma cells and decreased expression of them contributes to the progression of this disease.

Multiple Functions of Jab1 Are Required for Early Embryonic Development and Growth Potential in Mice

“…It is a tempting hypothesis that the Jab1-containing subcomplex is a part of the p27 regulatory mechanism in early to mid-G 1 , and CSN controls p27 through Skp2-SCF in late G 1 . Furthermore, high expression levels of Jab1 are observed in human cancers and are sometimes correlated with a poor prognosis and a low level of p27 (47)(48)(49)(50)(51)(52)(53)(54)(55)(56). Jab1ϩ/Ϫ cells and animals may help determine the role of Jab1 in the regulation of potential target molecules in cancer such as p27 and the pathologies that accompany their dysregulation.…”

“…Although Jab1 plays an essential role in phosphorylation, deneddylation, and translocation, it remains to be determined how these activities are regulated by the large CSN complex and possibly by the small complex. Furthermore, Jab1 was found to be highly expressed in human cancers (47)(48)(49)(50)(51)(52)(53)(54)(55)(56), which, in some cases, correlates with a poor prognosis and low level expression of the CDK inhibitor p27. To understand better the function of Jab1 in development, cell proliferation, and oncogenesis, we targeted the Jab1 locus by homologous recombination in ES cells.…”

p57Kip2 and Cancer: Time for a Critical Appraisal

“…p57 Kip2 was reduced in poorly differentiated and undifferentiated carcinomas (120). The same group investigated p57 Kip2 content in 49 cases of thyroid lymphoma and 10 cases of chronic thyroiditis, and they reported a significant reduction of p57 Kip2 protein in more than 50% of thyroid lymphoma cases (121). In 2007, however, Melck and colleagues (122) did not observe p57 Kip2 variation between 100 benign and 105 malignant thyroid lesions.…”

“…Three studies have been performed on the level of p57 Kip2 in thyroid cancers (120)(121)(122). Ito and colleagues (120) investigated p57 Kip2 content in different thyroid tumors.…”

Stable Form of JAB1 Enhances Proliferation and Maintenance of Hematopoietic Progenitors

“…Although a certain level of JAB1 is expressed in normally proliferating and in nonproliferating cells, an increase in JAB1 expression of severalfold is observed in a variety of human cancer cells, such as breast cancer (14,15), malignant lymphoma (16), ovarian tumor (17), melanoma (18), non-small cell lung cancer (19,20), laryngeal squamous cell carcinoma (21), and thyroid medullary carcinoma (22). In hepatocellular carcinoma (23), a high level of JAB1 is associated with an increase in the genomic DNA copy number of the Jab1 locus.…”