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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.

SUBMITTER: Curmi PA

PROVIDER: S-EPMC2363189 | biostudies-other | 2000 Jan

REPOSITORIES: biostudies-other

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

Curmi P A PA Noguès C C Lachkar S S Carelle N N Gonthier M P MP Sobel A A Lidereau R R Bièche I I

British journal of cancer 20000101 1

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, w ...[more]

PMID: 10638981

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Project description:Background: The Epithelial Cell Adhesion Molecule (EpCAM) has been shown to be strongly expressed in human breast cancer and cancer stem cells and its overexpression has been supposed to support tumor progression and metastasis. However, effects of EpCAM overexpression on normal breast epithelial cells have never been studied before. Therefore, we analyzed effects of transient adenoviral overexpression of EpCAM on proliferation, migration and differentiation of primary human mammary epithelial cells (HMECs). METHODS: HMECs were transfected by an adenoviral system for transient overexpression of EpCAM. Thereafter, changes in cell proliferation and migration were studied using a real time measurement system. Target gene expression was evaluated by transcriptome analysis in proliferating and polarized HMEC cultures. A Chicken Chorioallantoic Membrane (CAM) xenograft model was used to study effects on in vivo growth of HMECs. RESULTS: EpCAM overexpression in HMECs did not significantly alter gene expression profile of proliferating or growth arrested cells. Proliferating HMECs displayed predominantly glycosylated EpCAM isoforms and were inhibited in cell proliferation and migration by upregulation of p27KIP1 and p53. HMECs with overexpression of EpCAM showed a down regulation of E-cadherin. Moreover, cells were more resistant to TGF-beta1 induced growth arrest and maintained longer capacities to proliferate in vitro. EpCAM overexpressing HMECs xenografts in chicken embryos showed hyperplastic growth, lack of lumen formation and increased infiltrates of the chicken leukocytes. CONCLUSIONS: EpCAM revealed oncogenic features in normal human breast cells by, inducing resistance to TGF-beta1-mediated growth arrest and supporting a cell phenotype with longer proliferative capacities in vitro. EpCAM overexpression resulted in hyperplastic growth in vivo. Thus, we suggest that EpCAM acts as a prosurvival factor counteracting terminal differentiation processes in normal mammary glands. For each gene a representative transcript probe set was selected based on a score that combines average expression and variation of expression across all samples. Transcript probe sets with more than 4 probes were preferred. Differential expression analysis between EPCAM over-expressing and control cells (expressing GFP) was performed using a paired moderated t-test employing functions provided by Bioconductor's limma package. p-values were subsequently adjusted for multiple hypothesis testing using the method from Benjamini and Hochberg for a strong control of the false discovery rate.

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

Publications

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

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