The cell cycle in breast cancer

Abstract

Landberg, G. & Roos, G. The cell cycle in breast cancer. APMIS 105: 575-589, 1997. Breast cancer is a heterogeneous disease regarding morphology, invasive behavior, metastatic capacity, hormone receptor expression and clinical outcome. For prediction of prognosis, tumor cell kinetics is an important feature, traditionally evaluated by estimation of cell growth-associated parameters such as mitotic index, S-phase fraction and expression of proliferation coupled proteins, for example proliferating cell nuclear antigen (PCNA) and Ki-67 antigen. Recent data indicate that deregulation of the cell cycle can occur at different levels in cancer and that the "deregulation pattern" can be of clinical significance. In the present overview we give a short description of approaches used for cell proliferation assessments, whereafter more recent data on cell cycle deregulation are discussed. Alterations of importance in breast cancer include overexpression of cyclins D1 and E, down-regulation of cyclindependent kinase inhibitors, such as p16, and inactivation of the retinoblastoma and p53 tumor suppressor proteins.

Geographic Patterns of Advanced Breast Cancer in Los Angeles: Associations with Biological and Sociodemographic Factors (United States)

“…Women with a negative ER test result or with no ER test were more likely to be diagnosed with advanced disease than those with a positive test, particularly those with lobular tumors, consistent with an association of negative receptor status with poorer prognostic characteristics such as higher rates of cell proliferation and poorer cell differentiation [22,23,[25][26][27][28][47][48][49]. Knowledge of the progesterone receptor test results added little to the predictive power of the model.…”

“…For purposes of analysis, cases with borderline estrogen and progesterone receptor status (1% of total) were classified together with cases with unknown status or those who did not have the test; this group is referred to in the tables as ''unknown status''. Tumors that are positive for ER or PR are associated with favorable prognostic characteristics including evidence of tumor cell differentiation and a lower rate of cell proliferation [22][23][24][25][26][27][28].…”

Prognostic value of proliferation in invasive breast cancer: a review

“…[14][15][16][17][18][19] Cellular proliferation takes place Abbreviations: BrdU, bromodeoxyuridine; MAI, mitotic activity index; McM, minichromosome maintenance; PCNA, proliferating cell nuclear antigen through a defined process in which several phases can be recognised. From the resting (G0) phase they join the active cycling population after appropriate stimuli and enter the first gap (G1) phase.…”

Cyclin I is expressed in human breast cancer and closely associated with VEGF and KDR expression

“…Due to a potential function for cyclin I in tumorigenesis either linked to cell cycle functions or to other pathways, we screened for possible associations Diagnostic tumor samples were collected from 114 patients with breast carcinoma, immunohistochemically stained and analyzed for variables as described [15]. Cyclin I immunohistochemistry was done using the antibody described in [3] and the sections from the tissue microarray described in [12][13][14]16]. Microarrayed tumor sections were examined by two separate investigators and a classification into four grades (0-3) was applied representing lack of staining, weak staining, intermediate staining and strong staining, respectively [15].…”

“…This was possible because tissue sections were derived from microarrayed breast tumors that we had earlier used to determine protein levels of retinoblastoma protein, cyclin E, cyclin D1, p16, p21, p27 and p53 as well as c-erbB2, VEGF, and KDR [12][13][14]. Cyclin I was not associated with proliferation or the majority of cell cycle regulatory proteins including Rb-phosphorylation, cyclin E associated kinase activity or p53 mutations ( Table 2).…”