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Title: Modelling molecular mechanisms of breast cancer and invasion:lessons from the normal gland

Publication Date:
Research Org.:
Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
Sponsoring Org.:
USDOE Director. Office of Science. Biological andEnvironmental Research
OSTI Identifier:
Report Number(s):
R&D Project: 443180; BnR: KP1104010
DOE Contract Number:
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical Society Transactions; Journal Volume: 35; Journal Issue: pt1; Related Information: Journal Publication Date: 2007
Country of Publication:
United States

Citation Formats

Bissell, M.J. Modelling molecular mechanisms of breast cancer and invasion:lessons from the normal gland. United States: N. p., 2007. Web.
Bissell, M.J. Modelling molecular mechanisms of breast cancer and invasion:lessons from the normal gland. United States.
Bissell, M.J. Thu . "Modelling molecular mechanisms of breast cancer and invasion:lessons from the normal gland". United States. doi:.
title = {Modelling molecular mechanisms of breast cancer and invasion:lessons from the normal gland},
author = {Bissell, M.J.},
abstractNote = {},
doi = {},
journal = {Biochemical Society Transactions},
number = pt1,
volume = 35,
place = {United States},
year = {Thu Feb 01 00:00:00 EST 2007},
month = {Thu Feb 01 00:00:00 EST 2007}
  • The normal mammary gland and invasive breast cancer are both complex 'organs' composed of multiple cell types as well as extracellular matrix (ECM) in three-dimensional (3D) space. Conventionally, both normal and malignant breast cells are studied in vitro as two-dimensional (2D) monolayers of epithelial cells, which results in the loss of structure and tissue function. Many laboratories are now investigating regulation of signaling function in normal mammary gland using 3D cultures. However, it is important also to assay malignant breast cells ex vivo in a physiologically relevant environment to more closely mimic tumor architecture, signal transduction regulation and tumor behaviormore » in vivo. Here we present the potential of these 3D models for drug testing, target validation and guidance of patient selection for clinical trials. We argue also that in order to get full insight into the biology of the normal and malignant breast, and to create in vivo-like models for therapeutic approaches in humans, we need to continue to create more complex heterotypic models to approach the full context the cells encounter in the human body.« less
  • Purpose: Recent studies have raised concerns about exposure to low-dose ionizing radiation from medical imaging procedures. Little has been published regarding the relative exposure and risks associated with breast imaging techniques such as breast specific gamma imaging (BSGI), molecular breast imaging (MBI), or positron emission mammography (PEM). The purpose of this article was to estimate and compare the risks of radiation-induced cancer from mammography and techniques such as PEM, BSGI, and MBI in a screening environment. Methods: The authors used a common scheme for all estimates of cancer incidence and mortality based on the excess absolute risk model from themore » BEIR VII report. The lifetime attributable risk model was used to estimate the lifetime risk of radiation-induced breast cancer incidence and mortality. All estimates of cancer incidence and mortality were based on a population of 100 000 females followed from birth to age 80 and adjusted for the fraction that survives to various ages between 0 and 80. Assuming annual screening from ages 40 to 80 and from ages 50 to 80, the cumulative cancer incidence and mortality attributed to digital mammography, screen-film mammography, MBI, BSGI, and PEM was calculated. The corresponding cancer incidence and mortality from natural background radiation was calculated as a useful reference. Assuming a 15%-32% reduction in mortality from screening, the benefit/risk ratio for the different imaging modalities was evaluated. Results: Using conventional doses of 925 MBq Tc-99m sestamibi for MBI and BSGI and 370 MBq F-18 FDG for PEM, the cumulative cancer incidence and mortality were found to be 15-30 times higher than digital mammography. The benefit/risk ratio for annual digital mammography was >50:1 for both the 40-80 and 50-80 screening groups, but dropped to 3:1 for the 40-49 age group. If the primary use of MBI, BSGI, and PEM is in women with dense breast tissue, then the administered doses need to be in the range 75-150 MBq for Tc-99m sestamibi and 35 MBq-70 MBq for F-18 FDG in order to obtain benefit/risk ratios comparable to those of mammography in these age groups. These dose ranges should be achievable with enhancements to current technology while maintaining a reasonable examination time. Conclusions: The results of the dose estimates in this study clearly indicate that if molecular imaging techniques are to be of value in screening for breast cancer, then the administered doses need to be substantially reduced to better match the effective doses of mammography.« less
  • No abstract prepared.
  • Breast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2more » oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects-latency and tumor load-were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. In conclusion, our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.« less