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PTHrP and breast cancer: more than hypercalcemia and bone metastases.

ABSTRACT: Parathyroid hormone-related protein (PTHrP) causes hypercalcemia in cancer patients. PTHrP is required for normal breast development and has been shown to promote bone metastases from breast cancers. However, whether the protein also contributes to the formation of primary tumors has been unclear. Two recent papers suggest it may. First, a report in Nature Genetics identified the PTHrP locus as a new breast cancer susceptibility gene. Second, a paper in Journal of Clinical Investigation demonstrated that PTHrP promotes tumor growth and metastases in MMTV-PyMT mice. These studies implicate PTHrP in the development and growth of primary breast tumors and underscore the need for further research.

SUBMITTER: Boras-Granic K

PROVIDER: S-EPMC3446368 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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PTHrP and breast cancer: more than hypercalcemia and bone metastases.

Boras-Granic Kata K Wysolmerski John J JJ

Breast cancer research : BCR 20120425 2

Parathyroid hormone-related protein (PTHrP) causes hypercalcemia in cancer patients. PTHrP is required for normal breast development and has been shown to promote bone metastases from breast cancers. However, whether the protein also contributes to the formation of primary tumors has been unclear. Two recent papers suggest it may. First, a report in Nature Genetics identified the PTHrP locus as a new breast cancer susceptibility gene. Second, a paper in Journal of Clinical Investigation demonstr ...[more]

PMID: 22546075

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Project description:BackgroundBone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone.Methods/designThe B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases.DiscussionThe B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the potential of metabolomic profiles for risk assessment and early detection and the signalling pathways controlling the metastatic tumour microenvironment. There is substantial synergy between the four projects and it is hoped that this integrated program of research will advance our understanding of key aspects of bone metastases from breast cancer to improve the prevention, prediction, detection, and treatment of these lesions.

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PTHrP and breast cancer: more than hypercalcemia and bone metastases.

Publications

PTHrP and breast cancer: more than hypercalcemia and bone metastases.

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