A transforming growth factor beta 1 receptor type II mutation in ulcerative colitis-associated neoplasms

Souza, R. J. S.; Lei, Jiao; Yin, Jing; Appel, Rebecca; Zou, TT; Zhou, Xiaoping; Wang, Shigang; Rhyu, MG; Cymes, Karína; Chan, OO; Park, WS; Krasna, MJ; Bd, Greenwald; Cottrell, John R.; Abraham, JM; Simms, Lisa A.; Leggett, Barbara A.; Young, Joanne; Harpaz, Noam; Sj, Meltzer

doi:10.1016/s0016-5085(97)70217-8

Cited by 87 publications

(48 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mutation has been reported to occur in the coding poly(A) tract of the TGFbRII gene in numerous gastrointestinal tumours with microsatellite instability Souza et al, 1997;Myero et al, 1995) resulting in production of truncated RII protein.…”

Section: Discussionmentioning

confidence: 99%

Microsatellite instability in European hepatocellular carcinoma

et al. 1999

View full text Add to dashboard Cite

Genetic instability has been detected in many types of cancers but poorly investigated in hepatocellular carcinoma (HCC). We have studied the incidence of microsatellite instability (MI) at eight highly polymorphic microsatellite markers and the poly A tract BAT26 and tested for mutations at two sites of repetitive sequence (poly-A nucleotides 709 ± 718 and GT repeatnucleotides 1931 ± 1936) in the Transforming Growth Factor b (TGFb) type II receptor (RII) gene, in a group of 46 European HCCs and the surrounding nontumour tissue. This analysis showed that 63% of HCCs exhibit MI in at least one chromosome locus and 41% in two or more loci. No mutations of the TGFbRII gene were found in the MI positive tumours. No correlation was found with clinicopathological characteristics of the tumours such as cirrhosis, etiology, number of nodules, Edmondson's grade and vascular invasion. However, in patients who had a rearranged D16S402 microsatellite in their tumour, the recurrent disease and the number of nodules were signi®cantly higher than in the others (P50.005 and P50.02, respectively). We propose to consider D16S402 rearrangement in HCC as a prognostic factor to identify patients presenting a higher risk of recurrence.

show abstract

Section: Discussionmentioning

confidence: 99%

Microsatellite instability in European hepatocellular carcinoma

et al. 1999

View full text Add to dashboard Cite

show abstract

“…For example, epithelial cells secrete TGF-b1 as a latent precursor: this inactive form requires binding to IGFIIR in order for cleavage to its active growth-inhibitory state to occur (Kojima et al, 1993;Dennis and Rifkin, 1991). Unresponsiveness to the growth-limiting eects of TGF-b1 is common in colorectal carcinoma cell lines, and a prevalent mechanism underlying this resistance is mutation of the type II TGF-b1 receptor Parsons et al, 1995;Souza et al, 1997). However, an alternative mechanism freeing tumor cells from the growth-suppressive eect of TGF-b1 is`upstream' mutation of IGFIIR, with consequent failure to activate latent TGF-b1 (Massague, 1990).…”

Section: Introductionmentioning

confidence: 99%

Expression of the wild-type insulin-like growth factor II receptor gene suppresses growth and causes death in colorectal carcinoma cells

et al. 1999

View full text Add to dashboard Cite

The insulin-like growth factor II receptor (IGFIIR) has been implicated as a tumor suppressor gene in human malignancy. Frequent mutation, loss of heterozygosity, and microsatellite instability (MSI) directly aecting the IGFIIR gene have been reported in several primary human tumor types. However, to our knowledge, dynamic functional evidence of a growth-suppressive role for IGFIIR has not yet been provided. We identi®ed one MSI-positive colorectal carcinoma cell line, SW48, with monoallelic mutation in IGFIIR identical to that seen in primary colorectal carcinomas. A zinc-inducible construct containing the wild-type IGFIIR cDNA was stably transfected into SW48 cells. Growth rate and apoptosis were compared between zinc-treated, untreated, and untransfected cells. A twofold increase in IGFIIR protein expression was detected after zinc treatment in discrete clonal isolates of transfected SW48 cells. Moreover, zinc induction of exogenous wild-type IGFIIR expression reproducibly decreased growth rate and increased apoptosis. These data prove that wild-type IGFIIR functions as a growth suppressor gene in colorectal cancer cells and provide dynamic in vitro functional support for the hypothesis that IGFIIR is a human growth suppressor gene.

show abstract

“…It is present in the majority of HNPCC and approximately 10% of sporadic colorectal cancers (Ionov et al, 1993;Lothe et al, 1993;Thibodeau et al, 1993;Aaltonen et al, 1994), as well as in tumors arising in extracolonic sites such as the stomach (Rhyu et al, 1994). In addition to containing widespread microsatellite instability at anonymous sequences, most tumors with this mutator phenotype harbor frameshift mutations in coding mononucleotide repeat sequences in cancer related genes TGFb RII, IGF-IIR, BAX, hMSH3, hMSH6 and E2F-4 Souza et al, 1996Souza et al, , 1997aYoshitaka et al, 1996;Rampino et al, 1997;Yin et al, 1997b;Perucho, 1996). Accumulating evidence suggests that tumorigenic pathways, characterized on the one hand by allelic losses and on the other by microsatellite instability, represent alternative processes (reviewed in Kinzler and Vogelstein, 1996).…”

mentioning

confidence: 99%

Reciprocal relationship between the tumor suppressors p53 and BAX in primary colorectal cancers

et al. 1998

View full text Add to dashboard Cite

Though most colorectal cancers show allelic losses, a subset of colorectal cancers (microsatellite instability or MSI-positive cancers) develop numerous small insertion and deletion mutations in repetitive DNA. Some of these sequences occur in coding regions of cancer related genes which, when targeted by frameshift mutations, produce truncations in their protein product. Such a gene is the proapoptotic tumor suppressor, BAX, mutated by frameshifts within a polyG sequence in approximately 50% of MSI-positive colorectal cancers. BAX is directly transactivated by p53, a gene commonly mutated in colorectal cancers but not often in MSI-positive lesions. Here we sought to characterize the relationship between BAX and p53 by simultaneously analysing a selected series of 65 colorectal tumors for mutations in the entire coding regions of both genes. The tumors comprised 19 MSI-high, 12 MSI-low and 34 MSI-null cancers. Eight of 19 MSI-high sporadic colorectal cancers (42%) contained insertions and deletions at the polyG tract in the BAX gene. In addition, three somatic BAX missense mutations were identi®ed in two tumors. A single missense mutation was detected in an MSI-high tumor that also contained a frameshift microdeletion, and two missense mutations were identi®ed in an MSI-null tumor wild-type for p53. p53 mutations were detected in 5/12 MSI-low tumors (42%) and 12/34 MSI-null tumors (35%). Of signi®cance, no p53 mutations were detected in MSI-high tumors. This study demonstrates that a reciprocal relationship exists between p53 and BAX in sporadic colorectal cancers, and further supports the hypothesis that MSI-low tumors are biologically similar to MSI-null tumors.

show abstract

A transforming growth factor beta 1 receptor type II mutation in ulcerative colitis-associated neoplasms

Cited by 87 publications

References 3 publications

Microsatellite instability in European hepatocellular carcinoma

Microsatellite instability in European hepatocellular carcinoma

Expression of the wild-type insulin-like growth factor II receptor gene suppresses growth and causes death in colorectal carcinoma cells

Reciprocal relationship between the tumor suppressors p53 and BAX in primary colorectal cancers

Contact Info

Product

Resources

About