FGFR2 risk SNPs confer breast cancer risk by augmenting oestrogen responsiveness
The fibroblast growth factor receptor 2 (FGFR2) locus is consistently the top hit in genome-wide association studies for oestrogen receptor-positive (ER+) breast cancer. Yet, its mode of action continues to be controversial. Here, we employ a systems biology approach to demonstrate that signalling via FGFR2 counteracts cell activation by oestrogen. In the presence of oestrogen, the oestrogen receptor (ESR1) regulon (set of ESR1 target genes) is in an active state. However, signalling by FGFR2 is able to reverse the activity of the ESR1 regulon. This effect is seen in multiple distinct FGFR2 signalling model systems, across...
Source: Carcinogenesis - July 29, 2016 Category: Cancer & Oncology Authors: Campbell, T. M., Castro, M. A. A., de Santiago, I., Fletcher, M. N. C., Halim, S., Prathalingam, R., Ponder, B. A. J., Meyer, K. B. Tags: Original Manuscript Source Type: research
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(Source: Carcinogenesis)
Source: Carcinogenesis - July 29, 2016 Category: Cancer & Oncology Tags: Cover / Standing Material Source Type: research
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(Source: Carcinogenesis)
Source: Carcinogenesis - July 29, 2016 Category: Cancer & Oncology Tags: Cover / Standing Material Source Type: research
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(Source: Carcinogenesis)
Source: Carcinogenesis - July 29, 2016 Category: Cancer & Oncology Tags: Cover / Standing Material Source Type: research
Front_Cover
(Source: Carcinogenesis)
Source: Carcinogenesis - July 29, 2016 Category: Cancer & Oncology Tags: Cover / Standing Material Source Type: research
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(Source: Carcinogenesis)
Source: Carcinogenesis - July 29, 2016 Category: Cancer & Oncology Tags: Cover / Standing Material Source Type: research
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(Source: Carcinogenesis)
Source: Carcinogenesis - July 29, 2016 Category: Cancer & Oncology Tags: Cover / Standing Material Source Type: research
Hsp70 exerts oncogenic activity in the Apc mutant Min mouse model
Colorectal cancer (CRC) develops from colonic epithelial cells that lose expression of key tumor suppressor genes and/or gain expression of proproliferative and antiapoptotic genes like heat shock protein 70 (Hsp70). Heat shock protein 70 is overexpressed in CRC, but it is not known whether this is in response to the proteotoxic stress induced by transformation, or if it contributes to the process of transformation itself. Here, using the Apc Min/+ mouse model of CRC, we show that Hsp70 regulates mitogenic signaling in intestinal epithelial cells through stabilization of proteins involved in the receptor tyrosine kina...
Source: Carcinogenesis - July 6, 2016 Category: Cancer & Oncology Authors: Tao, Y., Messer, J. S., Goss, K. H., Hart, J., Bissonnette, M., Chang, E. B. Tags: Original Manuscript Source Type: research
Obesity promotes PhIP-induced small intestinal carcinogenesis in hCYP1A-db/db mice: involvement of mutations and DNA hypermethylation of Apc
Obesity is associated with an increased risk of cancer. To study the promotion of dietary carcinogen-induced gastrointestinal cancer by obesity, we employed 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to induce intestinal tumorigenesis in CYP1A-humanized (hCYP1A) mice, in which mouse Cyp1a1/1a2 was replaced with human CYP1A1/1A2. Obesity was introduced in hCYP1A mice by breeding with Leprdb/+ mice to establish the genetically induced obese hCYP1A-Leprdb/db mice or by feeding hCYP1A mice a high-fat diet. PhIP induced the formation of small intestinal tumors at the ages of weeks 28–40 in obese hCYP1A mice, b...
Source: Carcinogenesis - July 6, 2016 Category: Cancer & Oncology Authors: Wang, H., Liu, A., Kuo, Y., Chi, E., Yang, X., Zhang, L., Yang, C. S. Tags: Original Manuscript Source Type: research
Lipocalin 2 prevents oral cancer metastasis through carbonic anhydrase IX inhibition and is associated with favourable prognosis
In this study, we observed that LCN2 expression decreased in patients with OSCC and lymph node metastasis compared with that in patients without metastasis. A higher LCN2 expression correlated with the survival of patients with OSCC. Furthermore, LCN2 overexpression in OSCC cells reduced in vitro migration and invasion and in vivo metastasis, whereas its silencing induced an increase in cell motility. Mechanistically, LCN2 inhibited the cell motility of OSCC cells through hypoxia-inducible factor (HIF)-1α-dependent transcriptional inhibition of the carbonic anhydrase IX (CAIX). CAIX overexpression relieved the migrat...
Source: Carcinogenesis - July 6, 2016 Category: Cancer & Oncology Authors: Lin, C.-W., Yang, W.-E., Lee, W.-J., Hua, K.-T., Hsieh, F.-K., Hsiao, M., Chen, C.-C., Chow, J.-M., Chen, M.-K., Yang, S.-F., Chien, M.-H. Tags: Original Manuscript Source Type: research
Icaritin suppresses development of neuroendocrine differentiation of prostate cancer through inhibition of IL-6/STAT3 and Aurora kinase A pathways in TRAMP mice
In this study, we examined the mechanistic effects of a natural prenylflavonoid, icaritin (ICT), on neuroendocrine differentiation in IL-6-induced LNCaP cells and NEPC development in the male transgenic adenocarcinoma of the mouse prostate (TRAMP) model. TRAMP mice received daily intraperitoneal injection of ICT or vehicle. ICT induced apoptosis in prostate tumor, suppressed NEPC development and, accordingly, improved overall survival in TRAMP mice. Expression of neuroendocrine markers (synaptophysin) and androgen receptor in TRAMP mice and neuroendocrine-like LNCaP cells were inhibited by ICT. Suppression of neuroendocrin...
Source: Carcinogenesis - July 6, 2016 Category: Cancer & Oncology Authors: Sun, F., Zhang, Z. W., Tan, E. M., Lim, Z. L. R., Li, Y., Wang, X. C., Chua, S. E., Li, J., Cheung, E., Yong, E.-L. Tags: Original Manuscript Source Type: research
Comparison of hematological alterations and markers of B-cell activation in workers exposed to benzene, formaldehyde and trichloroethylene
Benzene, formaldehyde (FA) and trichloroethylene (TCE) are ubiquitous chemicals in workplaces and the general environment. Benzene is an established myeloid leukemogen and probable lymphomagen. FA is classified as a myeloid leukemogen but has not been associated with non-Hodgkin lymphoma (NHL), whereas TCE has been associated with NHL but not myeloid leukemia. Epidemiologic associations between FA and myeloid leukemia, and between benzene, TCE and NHL are, however, still debated. Previously, we showed that these chemicals are associated with hematotoxicity in cross-sectional studies of factory workers in China, which inclu...
Source: Carcinogenesis - July 6, 2016 Category: Cancer & Oncology Authors: Bassig, B. A., Zhang, L., Vermeulen, R., Tang, X., Li, G., Hu, W., Guo, W., Purdue, M. P., Yin, S., Rappaport, S. M., Shen, M., Ji, Z., Qiu, C., Ge, Y., Hosgood, H. D., Reiss, B., Wu, B., Xie, Y., Li, L., Yue, F., Freeman, L. E. B., Blair, A., Hayes, R. B Tags: Original Manuscript Source Type: research
Dose validation of PhIP hair level as a biomarker of heterocyclic aromatic amines exposure: a feeding study
Hair measurement of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a promising biomarker of exposure to this carcinogen formed in cooked meats. However, the dose relationship between normal range intake and hair levels and the modulating effects of CYP1A2 metabolism and hair melanin need to be evaluated. We conducted a randomized, cross-over feeding study among 41 non-smokers using ground beef cooked to two different levels of doneness, 5 days a week for 1 month. PhIP was measured by liquid chromatography/mass spectrometry in food (mean low dose = 0.72 µg/serving; mean high dose = 2.99 µg/serving), a...
Source: Carcinogenesis - July 6, 2016 Category: Cancer & Oncology Authors: Le Marchand, L., Yonemori, K., White, K. K., Franke, A. A., Wilkens, L. R., Turesky, R. J. Tags: Original Manuscript Source Type: research
Selected single-nucleotide polymorphisms in FOXE1, SERPINA5, FTO, EVPL, TICAM1 and SCARB1 are associated with papillary and follicular thyroid cancer risk: replication study in a German population
Several single-nucleotide polymorphisms (SNPs) have been associated with papillary and follicular thyroid cancer (PTC and FTC, respectively) risk, but few have replicated. After analyzing 17525 tag SNPs in 1129 candidate genes, we found associations with PTC risk in SERPINA5, FTO, HEMGN (near FOXE1) and other genes. Here, we report results from a replication effort in a large independent PTC/FTC case–control study conducted in Germany. We evaluated the best tagging SNPs from our previous PTC study and additionally included SNPs in or near FOXE1 and NKX2-1 genes, known susceptibility loci for thyroid cancer. We genoty...
Source: Carcinogenesis - July 6, 2016 Category: Cancer & Oncology Authors: Sigurdson, A. J., Brenner, A. V., Roach, J. A., Goudeva, L., Müller, J. A., Nerlich, K., Reiners, C., Schwab, R., Pfeiffer, L., Waldenberger, M., Braganza, M., Xu, L., Sturgis, E. M., Yeager, M., Chanock, S. J., Pfeiffer, R. M., Abend, M., Port, M Tags: Original Manuscript Source Type: research
High prevalence of luminal B breast cancer intrinsic subtype in Colombian women
Breast cancer is the most frequent malignancy in women worldwide. Distinct intrinsic subtypes of breast cancer have different prognoses, and their relative prevalence varies significantly among ethnic groups. Little is known about the prevalence of breast cancer intrinsic subtypes and their association with clinicopathological data and genetic ancestry in Latin Americans. Immunohistochemistry surrogates from the 2013 St. Gallen International Expert Consensus were used to classify breast cancers in 301 patients from Colombia into intrinsic subtypes. We analyzed the distribution of subtypes by clinicopathological variables. ...
Source: Carcinogenesis - July 6, 2016 Category: Cancer & Oncology Authors: Serrano-Gomez, S. J., Sanabria-Salas, M. C., Hernandez-Suarez, G., Garcia, O., Silva, C., Romero, A., Mejia, J. C., Miele, L., Fejerman, L., Zabaleta, J. Tags: Original Manuscript Source Type: research
