Mutant KRAS in aberrant crypt foci (ACF): Initiation of colorectal cancer?

Pretlow, Theresa P.; Pretlow, Thomas G.

doi:10.1016/j.bbcan.2005.06.002

Cited by 83 publications

(116 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…12 Increased i-NOS expression has been reported in dysplastic ACF, but not in hyperplastic ACF. 21 Other authors have failed to detect an increase in i-NOS in AOM-induced ACF, 32 and reduced i-NOS expression has even been reported in human ACF.…”

Section: Discussionmentioning

confidence: 99%

“…12 In this regard, some studies have focused on ACF, considered one of the earliest lesions in carcinogenesis but with a correlation with carcinogenesis not always straightforward. 30,31 According to some authors, carcinogeninduced ACF, as well as sporadic ACF in humans have COX-2 expression similar to normal mucosa.…”

Section: Discussionmentioning

confidence: 99%

“…To contextualize the MDF data within the various steps of colon carcinogenesis, the same determinations were performed in tumours harvested at a later time as well in ACF, which are well-characterized preneoplastic lesions. 12 We also set up conditions to isolate RNA from single MDF and determined i-NOS expression with RT-PCR experiments in a small separate set of MDF.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mucin‐depleted foci show strong activation of inflammatory markers in 1,2‐dimethylhydrazine‐induced carcinogenesis and are promoted by the inflammatory agent sodium dextran sulfate

Femia

Dolara

Luceri

et al. 2009

Intl Journal of Cancer

View full text Add to dashboard Cite

Mucin‐depleted foci (MDF), formed by dysplastic crypts devoid of mucins, have been identified in the colon of carcinogen‐treated rodents and in humans at high risk for colon cancer. The lack of the protective layer of mucus may cause inflammation which has been linked to colon carcinogenesis, therefore, the expression of markers such as cyclooxygenase‐2 (COX‐2), inducible nitric oxide synthase (i‐NOS) and macrophage infiltration was studied with immunohistochemistry (IH) in MDF harvested from F344 rats treated with the colon carcinogen 1,2‐dimethylhydrazine (DMH). The same determinations were performed in aberrant crypt foci (ACF) and, at a later time point, in tumours. A dramatic increase in COX‐2, i‐NOS and macrophage infiltration was observed in MDF but ACF showed a moderate increase compared with the paired normal mucosa. Tumours were positive for all the markers. RT‐PCR experiments demonstrated that i‐NOS RNA expression was increased in a set of MDF confirming the results obtained with immunohistochemistry. In an inflammation‐cancer experimental model [mice treated with azoxymethane (AOM) and dextran sodium sulphate (DSS)], we observed that DSS‐induced inflammation promoted MDF in a dose‐dependent manner, whereas ACF were not affected. In conclusion, we report here for the first time a strong activation of the inflammatory process in MDF, which may contribute to the further progression of MDF to tumours. © 2009 UICC

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Mucin‐depleted foci show strong activation of inflammatory markers in 1,2‐dimethylhydrazine‐induced carcinogenesis and are promoted by the inflammatory agent sodium dextran sulfate

Femia

Dolara

Luceri

et al. 2009

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…miR-487b eventually decreased the SRE transcription activity. Earlier studies have established the roles of KRAS-dependent signaling in enhancement of cell proliferation, invasion and metastasis in CRC (34,36). The mutation status of KRAS gene is one of the most essential factors for treatment strategy against CRC in the use of anti-EGFR antibody.…”

Section: Discussionmentioning

confidence: 99%

Identification of microRNA-487b as a negative regulator of liver metastasis by regulation of KRAS in colorectal cancer

Hata

Mokutani

Takahashi

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

Abstract.Recent studies have shown that microRNAs (miRNAs) are involved in the progression of colorectal cancer (CRC). The aim of this study is to identify a novel miRNA that especially relates to liver metastasis and to explore the underlying mechanism. Differentially expressed miRNAs were analyzed using microarray, in primary CRC tumors without metastasis (n=16), those with liver metastasis (n=12), and liver metastatic lesions (n=8). We found that miR-487b level decreased in liver metastatic lesions, and qRT-PCR confirmed the results in the validating cohort (n=134). Survival analysis indicated that high expression of miR-487b was associated with better prognosis. In vitro studies were also performed to investigate the functional significance of miR-487b in human CRC cell lines. miR-487b showed an inhibitory effect on cell proliferation and invasion of CRC cells. miR-487b downregulated KRAS and inhibited its downstream signal pathways, and the luciferase reporter assay revealed that miR-487b directly targeted LRP6, a receptor for WNT/β-catenin signaling. These findings showed that decrease in miR-487b was related with liver metastasis. Our data suggest a possibility that miR-487b may suppress metastasis of CRC progression through inhibition of KRAS.

show abstract

“…Several kallikreins, including KLK6, are either already in clinical use or are currently under investigation as serum biomarkers for cancer (Diamandis et al, 2003;Obiezu and Diamandis, 2005;Santin et al, 2005). K-RAS is often found to be an early mutation in colon cancer (Pretlow and Pretlow, 2005), and therefore a serum marker associated with mutant K-RAS could prove to be valuable. A study by Wan et al (2004) demonstrated that K-RAS mutations could be identified in fecal samples from approximately 57% of patients with colon cancer, with a small but non-significant difference between early-and late-stage disease.…”

Section: Discussionmentioning

confidence: 99%

Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells

Henkhaus

Gerner

Ignatenko

2008

BCHM

View full text Add to dashboard Cite

Kallikrein 6 (KLK6) is a trypsin-like serine peptidase whose relevance in various types of cancers is currently being explored. Previous studies have shown that KLK6 mRNA is upregulated in colon and gastric cancers; however, the regulatory mechanisms and phenotypic consequences of this upregulation are largely unknown. Activating K-RAS mutations are common in colon cancer, occurring in approximately 50% of cases. We have recently reported the upregulation of KLK6 mRNA in Caco2 human colon cancer cells stably transfected with a mutant K-RAS allele (K-RAS G12V ). In this study we examined the pattern of K-RAS-dependent KLK6 expression and secretion in colon cancer cells. Using pharmacological inhibitors of pathways downstream of K-RAS, we could show that the PI3K and p42/44 MAPK pathways play an important role in the induction of KLK6 in mutant K-RAS-expressing colon cancer cells. Increased KLK6 expression enhanced colon cancer cell migration through laminin and Matrigel. Inhibition of KLK6 using small interference RNA treatment or a specific KLK6 antibody in Caco2 cells stably expressing the mutant K-RAS and in SW480 cells carrying a mutation in the K-RAS oncogene resulted in a reduction in invasiveness through cell culture inserts. These data support the oncogenic role of KLK6 in colorectal cancer.

show abstract

Mutant KRAS in aberrant crypt foci (ACF): Initiation of colorectal cancer?

Cited by 83 publications

References 100 publications

Mucin‐depleted foci show strong activation of inflammatory markers in 1,2‐dimethylhydrazine‐induced carcinogenesis and are promoted by the inflammatory agent sodium dextran sulfate

Mucin‐depleted foci show strong activation of inflammatory markers in 1,2‐dimethylhydrazine‐induced carcinogenesis and are promoted by the inflammatory agent sodium dextran sulfate

Identification of microRNA-487b as a negative regulator of liver metastasis by regulation of KRAS in colorectal cancer

Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells

Contact Info

Product

Resources

About