Overexpression of stathmin in breast carcinomas points out to highly proliferative tumours

Abstract

We recently discovered that stathmin was overexpressed in a subgroup of human breast carcinomas. Stathmin is a cytosolic phosphoprotein proposed to act as a relay integrating diverse cell signalling pathways, notably during the control of cell growth and differentiation. It may also be considered as one of the key regulators of cell division for its ability to destabilize microtubules in a phosphorylation-dependent manner. To assess the significance of stathmin overexpression in breast cancer, we evaluated the correlation of stathmin expression, quantified by reverse transcription polymerase chain reaction, with several disease parameters in a large series of human primary breast cancer (n = 133), obtained in strictly followed up women, whose clinico-pathological data were fully available. In agreement with our preliminary survey, stathmin was found overexpressed in a subgroup of tumours (22%). In addition, overexpression was correlated to the loss of steroid receptors (oestrogen, P = 0.0006; progesterone, P = 0.008), and to the Scarff–Bloom–Richardson histopathological grade III (P = 0.002), this latter being ascribable to the mitotic index component (P = 0.02). Furthermore studies at the DNA level indicated that stathmin is overexpressed irrespective of its genomic status. Our findings raise important questions concerning the causes and consequences of stathmin overexpression, and the reasons of its inability to counteract cell proliferation in the overexpression group. © 2000 Cancer Research Campaign

Stathmin/Op18 is a novel mediator of vinblastine activity

“…This is the first report to provide a possible biophysical explanation for the increased sensitivity to Vinca alkaloids in cells over-expressing stathmin [12]. This mechanism could contribute to Vinca alkaloid selectivity for tumor cells in which stathmin is over-expressed compared to normal cells [7][8][9][10].…”

“…A number of reports have shown that stathmin is expressed at high levels in a wide variety of human cancers [7][8][9][10]. Furthermore, it has been observed that stathmin modifies the antimitotic efficiency of antitumor cancer drugs, such as vinblastine (VLB) [11,12].…”

Comprehensive gene expression profiling of anaplastic thyroid cancers with cDNA microarray of 25 344 genes

“…For its part, stathmin (Op18) is a member of a novel class of microtubule-destabilizing proteins that regulate the dynamics of microtubule polymerization and depolymerization (Mistry & Atweh 2002). Stathmin protein appears to have oncogenic potential, because it is widely expressed in various kinds of human cancers, including leukemia (Ghosh et al 1993), prostate cancer (Friedrich et al 1995) and breast cancer (Curmi et al 2000), and because inhibition of stathmin can decrease the rate of proliferation of K562 erythroleukemic cells (Luo et al 1994). In the clinical setting, some anti-cancer drug regimens are designed to inhibit microtubule assembly and arrest cells in mitosis, or to promote assembly of microtubules and stabilize tubulin polymers by preventing their depolymerization (Mistry & Atweh 2002).…”

Identification of novel targets for cancer therapy using expression proteomics

“…Indeed, an increased Op18 expression at both RNA and protein levels has been reported in a variety of cancers. 41,[59][60][61][62] We have identified a somatic Q18E mutation in Op18 in an esophageal adenocarcinoma. 63 Functional analyses of this mutation demonstrated that the mutant Op18 has transforming properties.…”