Growth control of normal and malignant breast epithelium

1989 ◽  
Vol 95 ◽  
pp. 89-106
Author(s):  
Marc E. Lippman ◽  
Robert B. Dickson
Keyword(s):  
Breast Cancer ◽  
Growth Factors ◽  
Cancer Progression ◽  
Growth Control ◽  
Mammary Epithelium ◽  
Mammary Epithelial ◽  
Hormonal Stimulation ◽  
Polypeptide Growth Factors ◽  
Malignant Breast ◽  
Genetic Mechanisms

SynopsisWe review information highlighting the multiple roles of both steroidal (primarily oestrogen) and polypeptide regulators of mammary epithelial cell growth, emphasising the work of our laboratory. Effects of both classes of hormones are complex and involve multiple interactions with non-tumour, host tissue. Oestrogen may induce growth regulatory polypeptide growth factors and interact with them in hormone dependent breast cancer. Progression of hormone-dependent breast cancer to hormone independence may involve multiple genetic mechanisms of oncogene activation, loss of the oestrogen receptor, or loss of hormone responsivity of other gene products. Initial carcinogenesis and progression of mammary epithelium to cancer probably also requires both proliferative stimuli (oestrogen, polypeptide growth factors) and genetic damage, leading to qualitatively different hormonal responses (hormone responsive cancer). Future therapies should be designed to block hormonal stimulation better and to interfere with necessary activated or induced components of malignant progression such as oncogenes or polypeptide growth factors receptor systems.

scholarly journals Regulation of Epithelial-Mesenchymal Transition in Breast Cancer Cells by Cell Contact and Adhesion

2015 ◽  
Vol 14s3 ◽  
pp. CIN.S18965 ◽  
Author(s):  
Magdalena A. Cichon ◽  
Celeste M. Nelson ◽  
Derek C. Radisky
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Rna Splicing ◽  
Epithelial Mesenchymal Transition ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Cell Contact ◽  
Mesenchymal Transition ◽  
Matrix Metalloproteinase 3 ◽  
Expression Of Genes

Epithelial-mesenchymal transition (EMT) is a physiological program that is activated during cancer cell invasion and metastasis. We show here that EMT-related processes are linked to a broad and conserved program of transcriptional alterations that are influenced by cell contact and adhesion. Using cultured human breast cancer and mouse mammary epithelial cells, we find that reduced cell density, conditions under which cell contact is reduced, leads to reduced expression of genes associated with mammary epithelial cell differentiation and increased expression of genes associated with breast cancer. We further find that treatment of cells with matrix metalloproteinase-3 (MMP-3), an inducer of EMT, interrupts a defined subset of cell contact-regulated genes, including genes encoding a variety of RNA splicing proteins known to regulate the expression of Rac1b, an activated splice isoform of Rac1 known to be a key mediator of MMP-3-induced EMT in breast, lung, and pancreas. These results provide new insights into how MMPs act in cancer progression and how loss of cell-cell interactions is a key step in the earliest stages of cancer development.

scholarly journals Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer

2017 ◽  
Author(s):  
Lucy Ireland ◽  
Almudena Santos ◽  
Fiona Campbell ◽  
Carlos Figueiredo ◽  
Lesley Ellies ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factors ◽  
Cancer Progression ◽  
Invasive Breast Cancer ◽  
Metastatic Breast ◽  
Advanced Tumor Stage ◽  
Breast Cancer Patients ◽  
Advanced Tumor ◽  
Potential Biomarker ◽  
Insulin Like Growth Factors

ABSTRACTBreast cancer remains the leading cause of cancer death in women due to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumours. 75% of breast cancer patients show activation of Insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in a pre-clinical breast cancer model compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation.

scholarly journals Carcinoma-Associated Fibroblasts Promote Growth of Sox2-Expressing Breast Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3435
Author(s):  
Angela Dittmer ◽  
Jürgen Dittmer
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Growth Control ◽  
B Cell Lymphoma ◽  
Fold Increase ◽  
Breast Cancer Cell Lines ◽  
Sox2 Expression ◽  
Long Term Treatment ◽  
Carcinoma Associated Fibroblasts

CAFs (Carcinoma-associated fibroblasts) play an important role in cancer progression. For instance, they promote resistance to anti-estrogens, such as fulvestrant. Here, we show that, in ERα-positive breast cancer cell lines, the cocktail of factors secreted by CAFs (CAF-CM) induce the expression of the embryonal stem cell transcription factor Sox2 (sex determining region Y (SRY)-box 2). Long-term exposure to CAF-CM was able to give rise to very high Sox2 levels both in the absence and presence of fulvestrant. IL-6 (interleukin-6), a major component of CAF-CM, failed to raise Sox2 expression. In MCF-7 sublines established in the presence of CAF-CM, almost all cells showed Sox2 expression, whereas long-term treatment of T47D cells with CAF-CM resulted in a ~60-fold increase in the proportions of two distinct populations of Sox2 high and low expresser cells. Exposure of BT474 cells to CAF-CM raised the fraction of Sox2 high expresser cells by ~3-fold. Cell sorting based on CD44 and CD24 expression or ALDH (aldehyde dehydrogenase) activity revealed that most Sox2 high expresser cells were not CD44hi/CD24lo- or ALDH-positive cells suggesting that they were not CSCs (cancer stem cells), though CD44 played a role in Sox2 expression. Functionally, Sox2 was found to protect CAF-CM-treated cells against apoptosis and to allow higher growth activity in the presence of fulvestrant. Mechanistically, the key drivers of Sox2 expression was found to be STAT3 (Signal transducer and activator of transcription 3), Bcl-3 (B-cell lymphoma 3) and the PI3K (Phosphoinositide 3-kinase)/AKT pathway, whose activities/expression can all be upregulated by CAF-CM. These data suggest that CAF-CM induces Sox2 expression in non-CSCs by activating proteins involved in growth control and drug resistance, leading to higher protection against apoptosis.

scholarly journals Akt1 governs breast cancer progression in vivo

2007 ◽  
Vol 104 (18) ◽  
pp. 7438-7443 ◽  
Author(s):  
Xiaoming Ju ◽  
Sanjay Katiyar ◽  
Chenguang Wang ◽  
Manran Liu ◽  
Xuanmao Jiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Lung Metastases ◽  
Three Dimensional ◽  
Mammary Tumorigenesis ◽  
Mammary Epithelial ◽  
Serine Threonine Kinase ◽  
Epithelial Tumor ◽  
Induced Changes

The serine threonine kinase Akt1 has been implicated in the control of cellular metabolism, survival and growth. Here, disruption of the ubiquitously expressed member of the Akt family of genes, Akt1, in the mouse demonstrates a requirement for Akt1 in ErbB2-induced mammary tumorigenesis. Akt1 deficiency delayed tumor growth and reduced lung metastases, correlating with a reduction in phosphorylation of the Akt1 target, tuberous sclerosis 2 (TSC2) at Ser-939. Akt1-deficient mammary epithelial tumor cells (MEC) were reduced in size and proliferative capacity, with reduced cyclin D1 and p27KIP1 abundance. Akt1 deficiency abrogated the oncogene-induced changes in polarization of MEC in three-dimensional culture and reverted oncogene-induced relocalization of the phosphorylated ezrin–radixin–moesin proteins. Akt1 increased MEC migration across an endothelial cell barrier, enhancing the persistence of migratory directionality. An unbiased proteomic analysis demonstrated Akt1 mediated MEC migration through paracrine signaling via induction of expression and secretion of CXCL16 and MIP1γ. Akt1 governs MEC polarity, migratory directionality and breast cancer onset induced by ErbB2 in vivo.

scholarly journals Roles for Growth Factors in Cancer Progression

Physiology ◽  
2010 ◽  
Vol 25 (2) ◽  
pp. 85-101 ◽  
Author(s):  
Esther Witsch ◽  
Michael Sela ◽  
Yosef Yarden
Keyword(s):  
Growth Factors ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Tumor Biology ◽  
Physiological Conditions ◽  
Downstream Signaling ◽  
Activating Mutations ◽  
Extracellular Signals ◽  
Polypeptide Growth Factors ◽  
Oncogenic Mutations

Under physiological conditions, cells receive fate-determining signals from their tissue surroundings, primarily in the form of polypeptide growth factors. Integration of these extracellular signals underlies tissue homeostasis. Although departure from homeostasis and tumor initiation are instigated by oncogenic mutations rather than by growth factors, the latter are the major regulators of all subsequent steps of tumor progression, namely clonal expansion, invasion across tissue barriers, angiogenesis, and colonization of distant niches. Here, we discuss the relevant growth factor families, their roles in tumor biology, as well as the respective downstream signaling pathways. Importantly, cancer-associated activating mutations that impinge on these pathways often relieve, in part, the reliance of tumors on growth factors. On the other hand, growth factors are frequently involved in evolvement of resistance to therapeutic regimens, which extends the roles for polypeptide factors to very late phases of tumor progression and offers opportunities for cancer therapy.

scholarly journals POSSIBILITIES FOR PREGNANCIES AND DELIVERIES IN SUCCESSION TO THE TREATMENT OF BREAST CANCER

2017 ◽  
Vol 4 (3) ◽  
pp. 149-153
Author(s):  
A. D Zikiryakhodzhaev ◽  
O. V Novikova ◽  
Elena A. Rasskazova
Keyword(s):  
Breast Cancer ◽  
Breast Neoplasms ◽  
Cancer Progression ◽  
Subsequent Pregnancy ◽  
Young Age ◽  
Breast Cancer Progression ◽  
Pregnancy And Lactation ◽  
Malignant Breast ◽  
Ovarian Lesion

In the article there is presented information about 9 patients of young age who delivered a child after the treatment in the P.A. Herzen Moscow Research Oncological Institute for malignant breast neoplasms. Oncological aspects of the treatment in patients, data on subsequent pregnancy and lactation were analyzed in detail. The length of the follow-up period for patients and children amounted to 12 to 84 months. Only one (11.1%) of the nine patients had breast cancer progression after delivery in the form of a metastatic ovarian lesion. Dynamic following up this group of patients is carried out.

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