Illegitimate Villin Transcripts in Normal Bone Marrow Precludes Detection of Colon Cancer Micrometastases

Salbe, C.; Crémoux, Patricia de; Bonneton, C.; Manet, S.; Almeida, Anna; Magdelénat, H.; Bourstyn, E.; Robine, Sylvie

doi:10.1177/172460080001500107

Cited by 8 publications

(4 citation statements)

References 8 publications

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“…''Illegitimate'' Villin transcripts have been found in normal bone marrow (31). Cre production in bone marrow followed by circulation of hematologic cells that contain the rearranged allele may explain the presence of low levels of rearranged RbD19 allele in tissues not expected to have Villin promoter activity during embryogenesis, such as tissue precursors for spleen, heart, and tail.…”

Section: Discussionmentioning

confidence: 99%

Inactivation of Conditional Rb by Villin-Cre Leads to Aggressive Tumors outside the Gastrointestinal Tract

Kucherlapati¹,

Nguyen²,

Bronson

et al. 2006

Cancer Research

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We have crossed mice carrying the conditional Rb tm2Brn allele with a constitutive Villin-Cre transgenic mouse. The Villin promoter in these animals is highly expressed in adult intestine and kidney proximal tubules and is expressed in the gut and nephros anlagen during embryogenesis. We report here that these mice develop tumors between 12 and 17 months old outside the gastrointestinal (GI) tract. A high penetrance of pituitary tumors and medullar carcinoma of the thyroid is observed with a lower incidence of hyperplasia of pulmonary neuroendocrine cells and aggressive liver, bile duct, stomach, oral cavity tumors, and lipomas. Rb rearrangement due to ectopic Villin promoter activity in neural crest or neural crest stem cells during embryogenesis is most likely responsible for the medullar carcinoma of the thyroid phenotype. The aggressive nature of the medullar carcinoma of the thyroid and its ability to metastasize to unusual sites make the model suitable for the study of tumor progression and mechanism of metastasis. Observed sites of metastasis include the stomach, small intestine, liver, lung, kidney, pancreas, spleen, bone marrow, salivary gland, fat, lymph nodes, and dorsal root ganglion. Because the Villin promoter is highly active throughout the GI and in the nephros anlagen during development, we find that Rb inactivation is not sufficient to initiate tumorigenesis in the GI or kidneys in mice. (Cancer Res 2006; 66(7): 3576-83)

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Section: Discussionmentioning

confidence: 99%

Inactivation of Conditional Rb by Villin-Cre Leads to Aggressive Tumors outside the Gastrointestinal Tract

Kucherlapati¹,

Nguyen²,

Bronson

et al. 2006

Cancer Research

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“…The phenomenon was firstly identified by Chelly and colleagues (1989) and has so far been described for almost all of the candidate tissue-specific target genes, including CK8 (Traweek et al, 1993), CK18 (Traweek et al, 1993), CK19 (Dingemans et al, 1997), prostata-specific antigen (McIntyre et al, 2000;Smith et al, 1995), and surfactant protein B (Betz et al, 1995). Only a few quantitative evaluations of illegitimate transcription in bone marrow have been performed so far (Salbe et al, 2000;Slade et al, 1999). Like previously performed semiquantitative evaluations, they report on rather unstable levels of background transcription for each target gene and primer set.…”

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confidence: 99%

Transcription of Cytokeratins 8, 18, and 19 in Bone Marrow and Limited Expression of Cytokeratins 7 and 20 by Carcinoma Cells: Inherent Limitations for RT-PCR in the Detection of Isolated Tumor Cells

Dimmler

Gerhards

Betz

et al. 2001

Laboratory Investigation

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SUMMARY:The suitability of "real-time" quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of isolated carcinoma cells in bone marrow was investigated by evaluating the expression of cytokeratin (CK)7, CK8, CK18, CK19, and CK20 in 17 gastrointestinal cancer cell lines, 64 control bone marrow specimens from noncancer patients, and 30 bone marrow specimens from patients with gastric or colorectal cancer. RT-PCR products for CK8 and CK18 were detected in all cancer cell lines, but only 16, 5, and 11 cell lines provided evidence for CK19, CK7, and CK20 transcription. Variable numbers of bone marrow specimens from noncancer patients demonstrated background transcription of CK8 (78.1%), CK18 (95.3%), CK19 (35.9%), CK20 (29.6%), and CK7 (16.7%). Maximal background transcription for CK8, CK18, and CK19 ranged from 52.2 to 56.1 copies/10 3 copies glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the corresponding values of 0.06 and 0.76 copies for CK7 and CK20 being distinctly lower. When maximal background values were used as a threshold value to define positivity in tumor cell dilution experiments, sensitivity levels of one tumor cell in 10 4 bone marrow cells were determined for CK7 and CK20 RT-PCR assays. Maximal background expression values of the different CKs as obtained in the control series were exceeded once (CK20), twice (CK18 and CK19), and 18 times (CK7) in bone marrow specimens from cancer patients, with none of these specimens exceeding the maximal background expression value of CK8. We conclude that RT-PCR for CK8, CK18, and CK19 cannot be recommended for the detection of isolated tumor cells in bone marrow of cancer patients. On the other side, the limited number of gastric and colorectal cancer cell lines expressing CK7 and CK20 indicates that assay sensitivity for these CKs might be limited because of their selective expression by carcinoma cells. (Lab Invest 2001, 81:1351-1361.

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“…RT-PCR has been described as a highly sensitive assay for the detection of transcripts as specific markers for normal and tumoral colon tissue [21] . Only the cDNA coding for these two genes from the human tumor cells implanted in the host tissues, and not the homologous genes of murine origin, were amplified (see tumor and brain in fig.…”

Section: Rt-pcr Analysis Of Metastasis Efficiency In Primary Tumorsmentioning

confidence: 99%

Heterogeneous Metastasis Efficiency of Isogenic Orthotopic Colon Cancer Xenografts Reveals Distinctive Gene Expression Profiles

Abal¹,

Fsihi²,

Bras-Gonçalves³

et al. 2007

Tumor Biol

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Hepatic and lung metastases are the leading causes of mortality and major indicators of aggressiveness in colorectal cancer. The underlying molecular mechanisms contributing to the development of metastasis are still unclear. Here, we designed a novel approach to explore gene expression profiles associated with metastasis in human colorectal cancer (hCRC). A series of ten isogenic tumors from three different hCRC models were orthotopically implanted into nude mice. In these series, we analyzed the contribution of dynamic heterogeneity, independently of any intrinsic gene expression program predictive of metastasis. When screened for the presence of disseminated tumor cells in the lung and liver, as the most common host tissues for hCRC metastases, both high- and low-metastatic efficient tumors were found among these isogenic orthotopic series. The metastasis-specific cDNA macroarray analysis of 96 genes, in both tumor populations for each of the three hCRC models, characterized a common differential gene expression within a small group of genes. Our results suggest that, independently of a gene expression profile predictive of metastasis, the progressive acquisition of additional alterations occurs during hCRC tumorigenesis. This dynamic process might determine tumor progression, namely the metastasis dissemination.

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Illegitimate Villin Transcripts in Normal Bone Marrow Precludes Detection of Colon Cancer Micrometastases

Cited by 8 publications

References 8 publications

Inactivation of Conditional Rb by Villin-Cre Leads to Aggressive Tumors outside the Gastrointestinal Tract

Inactivation of Conditional Rb by Villin-Cre Leads to Aggressive Tumors outside the Gastrointestinal Tract

Transcription of Cytokeratins 8, 18, and 19 in Bone Marrow and Limited Expression of Cytokeratins 7 and 20 by Carcinoma Cells: Inherent Limitations for RT-PCR in the Detection of Isolated Tumor Cells

Heterogeneous Metastasis Efficiency of Isogenic Orthotopic Colon Cancer Xenografts Reveals Distinctive Gene Expression Profiles

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