Engineering Transcription Factors in Breast Cancer Stem Cells

Blancafort, Pilar; Juarez, Karla Oyuky; Stolzenburg, Sabine; Beltran, Adriana S.

doi:10.5772/23788

Cited by 2 publications

(2 citation statements)

References 139 publications

(164 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously found that Trp53 , Bmp7 , Ctnnb1 , and Bmp10 identified Ingenuity canonical pathways for basal cell carcinoma signaling and role of NANOG in mammalian embryonic stem cell pluripotency [ 6 ]. This suggests that the similarity between HFD early tumors and basal-like breast cancer [ 23 ] is reiterated in the HFD-LFD early tumors. In our prior studies [ 6 ], Trp53 , Ctnnb1 , Ccnd2, Brca1 , and Apaf1 also identified Ingenuity canonical pathways for p53 signaling and GADD45 signaling.…”

Section: Discussionmentioning

confidence: 99%

Puberty-specific promotion of mammary tumorigenesis by a high animal fat diet

et al. 2015

View full text Add to dashboard Cite

IntroductionIncreased animal fat consumption is associated with increased premenopausal breast cancer risk in normal weight, but not overweight, women. This agrees with our previous findings in obesity-resistant BALB/c mice, in which exposure to a high saturated animal fat diet (HFD) from peripuberty through adulthood promoted mammary tumorigenesis. Epidemiologic and animal studies support the importance of puberty as a life stage when diet and environmental exposures affect adult breast cancer risk. In this study, we identified the effects of peripubertal exposure to HFD and investigated its mechanism of enhancing tumorigenesis.MethodsThree-week-old BALB/c mice fed a low-fat diet (LFD) or HFD were subjected to 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis. At 9 weeks of age, half the mice on LFD were switched to HFD (LFD-HFD group) and half the mice on HFD were switched to LFD (HFD-LFD group). Tumor gene expression was evaluated in association with diet and tumor latency.ResultsThe peripubertal HFD reduced the latency of DMBA-induced mammary tumors and was associated with tumor characteristics similar to those in mice fed a continuous HFD. Notably, short-latency tumors in both groups shared gene expression characteristics and were more likely to have adenosquamous histology. Both HFD-LFD and continuous HFD tumors showed similar gene expression patterns and early latency. Adult switch from HFD to LFD did not reverse peripubertal HFD tumor promotion. Increased proliferation, hyperplasia, and macrophages were present in mammary glands before tumor development, implicating these as possible effectors of tumor promotion. Despite a significant interaction between pubertal diet and carcinogens in tumor promotion, peripubertal HFD by itself produced persistent macrophage recruitment to mammary glands.ConclusionsIn obesity-resistant mice, peripubertal HFD is sufficient to irreversibly promote carcinogen-induced tumorigenesis. Increased macrophage recruitment is likely a contributing factor. These results underscore the importance of early life exposures to increased adult cancer risk and are consistent with findings that an HFD in normal weight premenopausal women leads to increased breast cancer risk. Notably, short-latency tumors occurring after peripubertal HFD had characteristics similar to human basal-like breast cancers that predominantly develop in younger women.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0646-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Puberty-specific promotion of mammary tumorigenesis by a high animal fat diet

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Provocatively, altered expression of a partially overlapping set of genes, Trp53 , Bmp7 , Ctnnb1 , and Bmp10 , identified the Basal Cell Carcinoma signaling and Role of NANOG in Mammalian Stem Cell Pluripotency pathways. This suggests similarity between the HFD-E tumors and breast tumors displaying stem and/or progenitor cell characteristics, such as basal-like breast cancer [ 81 ]. The downregulation of luminal epithelial makers, Krt8 and 18, in HFD-E tumors is also consistent with this.…”

Section: Discussionmentioning

confidence: 99%

Pubertal high fat diet: effects on mammary cancer development

et al. 2013

View full text Add to dashboard Cite

IntroductionEpidemiological studies linking dietary fat intake and obesity to breast cancer risk have produced inconsistent results. This may be due to the difficulty of dissociating fat intake from obesity, and/or the lack of defined periods of exposure in these studies. The pubertal mammary gland is highly sensitive to cancer-causing agents. We assessed how high fat diet (HFD) affects inflammation, proliferative, and developmental events in the pubertal gland, since dysregulation of these can promote mammary tumorigenesis. To test the effect of HFD initiated during puberty on tumorigenesis, we utilized BALB/c mice, for which HFD neither induces obesity nor metabolic syndrome, allowing dissociation of HFD effects from other conditions associated with HFD.MethodsPubertal BALB/c mice were fed a low fat diet (12% kcal fat) or a HFD (60% kcal fat), and subjected to carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis.ResultsHFD elevated mammary gland expression of inflammatory and growth factor genes at 3 and 4 weeks of diet. Receptor activator of nuclear factor kappa-B ligand (RANKL), robustly induced at 4 weeks, has direct mitogenic activity in mammary epithelial cells and, as a potent inducer of NF-κB activity, may induce inflammatory genes. Three weeks of HFD induced a transient influx of eosinophils into the mammary gland, consistent with elevated inflammatory factors. At 10 weeks, prior to the appearance of palpable tumors, there were increased numbers of abnormal mammary epithelial lesions, enhanced cellular proliferation, increased growth factors, chemokines associated with immune-suppressive regulatory T cells, increased vascularization, and elevated M2 macrophages. HFD dramatically reduced tumor latency. Early developing tumors were more proliferative and were associated with increased levels of tumor-related growth factors, including increased plasma levels of HGF in tumor-bearing animals. Early HFD tumors also had increased vascularization, and more intra-tumor and stromal M2 macrophages.ConclusionsTaken together in this non-obesogenic context, HFD promotion of inflammatory processes, as well as local and systemically increased growth factor expression, are likely responsible for the enhanced tumorigenesis. It is noteworthy that although DMBA mutagenesis is virtually random in its targeting of genes in tumorigenesis, the short latency tumors arising in animals on HFD showed a unique gene expression profile, highlighting the potent overarching influence of HFD.

show abstract

Engineering Transcription Factors in Breast Cancer Stem Cells

Cited by 2 publications

References 139 publications

Puberty-specific promotion of mammary tumorigenesis by a high animal fat diet

Puberty-specific promotion of mammary tumorigenesis by a high animal fat diet

Pubertal high fat diet: effects on mammary cancer development

Contact Info

Product

Resources

About