Increased Expression of Tumor-Associated Trypsin Inhibitor, TATI, in Prostate Cancer and in Androgen-Independent 22Rv1 Cells

Paju, Annukka; Hotakainen, Kristina; Cao, Yue; Laurila, Timo; Gadaleanu, Virgil; Hemminki, Akseli; Stenman, Ulf‐Hǎkan; Bjartell, Anders

doi:10.1016/j.eururo.2007.01.096

Cited by 74 publications

(69 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Increased levels of trypsinogen, tumor-associated trypsinogens, trypsin and its inhibitor TATI correlate with the malignancy of human solid tumors (Nyberg et al, 2006). The presence of TATI in tumors is a marker of adverse prognosis for hepatocellular carcinoma (HCC), bladder, kidney and mucinous ovarian cancers (Stenman, 2002;Antila et al, 2006;Lee et al, 2007;Paju et al, 2007). In patients with stage III and IV ovarian cancers, TATI tissue expression and elevated TATI concentration in serum were associated with adverse cancer-specific and progression-free survival (Paju et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Autocrine induction of invasion and metastasis by tumor-associated trypsin inhibitor in human colon cancer cells

et al. 2008

View full text Add to dashboard Cite

From the conditioned medium of the human colon carcinoma cells, HT-29 5M21 (CM-5M21), expressing a spontaneous invasive phenotype, tumor-associated trypsin inhibitor (TATI) was identified and characterized by proteomics, cDNA microarray approaches and functional analyses. Both CM-5M21 and recombinant TATI, but not the K18Y-TATI mutant at the protease inhibitor site, trigger collagen type I invasion by several human adenoma and carcinoma cells of the colon and breast, through phosphoinositide-3-kinase, protein kinase C and Rho-GTPases/Rho kinase-dependent pathways. Conversely, the proinvasive action of TATI in parental HT29 cells was alleviated by the TATI antibody PSKAN2 and the K18Y-TATI mutant. Stable expression of K18Y-TATI in HT-29 5M21 cells downregulated tumor growth, angiogenesis and the expression of several metastasisrelated genes, including CSPG4 (13.8-fold), BMP-7 (9.7-fold), the BMP antagonist CHORDIN (5.2-fold), IGFBP-2 and IGF2 (9.6-and 4.6-fold). Accordingly, ectopic expression of KY-TATI inhibited the development of lung metastases from HT-29 5M21 tumor xenografts in immunodeficient mice. These findings identify TATI as an autocrine transforming factor potentially involved in early and late events of colon cancer progression, including local invasion of the primary tumor and its metastatic spread. Targeting TATI, its molecular partners and effectors may bring novel therapeutic applications for high-grade human solid tumors in the digestive and urogenital systems.

show abstract

Section: Discussionmentioning

confidence: 99%

Autocrine induction of invasion and metastasis by tumor-associated trypsin inhibitor in human colon cancer cells

et al. 2008

View full text Add to dashboard Cite

show abstract

“…ERG reprime a NKX3.1 directamente mediante la unión a su promotor e indirectamente a través de la inducción de la EZH2, puesto que éste es un factor clave en el silenciamiento transcripcional del NKX3.1 (Kunderfranco et al, 2010). En cuanto a SPINK-1, varios estudios han sugerido que sus niveles de mRNA se asocian a un subtipo agresivo asociado a recurrencia bioquímica con ausencia de TMPRSS2-ERG (Paju et al, 2007;Tomlins et al, 2008;Jhavar et al, 2009;Leinonen et al, 2010;Grupp et al, 2013;Leinonen et al, 2013;Lippolis et al, 2013), pero otros trabajos afirman que no hay relación (Grupp et al, 2013;Lippolis et al, 2013;Flavin et al, 2014). Este tipo de resultados resalta la importancia de realizar más estudios que logren determinar la utilidad clínica de estos biomarcadores.…”

Section: Discussionunclassified

“…Las fusiones TMPRSS2-ERG que conducen a una sobreexpresión de ERG, están presentes en 50 % de los casos y se consideran un evento temprano en la carcinogénesis, presente en una proporción de las lesiones preneoplásicas denominadas Neoplasia Intraepitelial Prostática de Alto Grado (HGPIN por sus siglas en inglés) (Attard et al, 2008;Park et al, 2010). El inhibidor de serina peptidasa, Kazal tipo 1 (SPINK1) es una proteína secretada que se sobreexpresa específicamente en un subconjunto de cánceres con ausencia de la fusiones TMPRSS2-ERG (Paju et al, 2007;Tomlins et al, 2008;Leinonen et al, 2010;Leinonen et al, 2013;Lippolis et al, 2013) y se asocia con una disminución de la supervivencia (Ateeq et al, 2011).…”

Section: Introductionunclassified

Estandarización del protocolo para la detección de las fusiones TMPRSS2:ERG y de la expresión de los genes EZH2, SPINK-1 y NKX3.1 en cáncer de próstata (CaP)

Moreno

López

2016

Acta biol. Colomb.

View full text Add to dashboard Cite

Associate Editor: Argel Aguilar-Valles.Citation/Citar este artículo como: Segura Moreno YY, Serrano López ML. Estandarización del protocolo para la detección de las fusiones TMPRSS2:ERG y de la expresión de los genes EZH2, SPINK-1 y NKX3.1 en cáncer de próstata (CaP RESUMENEn la actualidad no existe una herramienta que permita diferenciar pacientes con cáncer de próstata (CaP) de mal pronóstico de aquellos con enfermedad indolente que sólo requieren un seguimiento controlado de la enfermedad. Debido a la coexistencia de diferentes focos premalignos y malignos en el CaP, el entendimiento sobre el proceso de carcinogénesis requiere de un mejor conocimiento. Actualmente, la heterogeneidad morfológica en CaP es evaluada con la puntuación de Gleason, la cual está fuertemente relacionada con el pronóstico de la enfermedad, sin embargo, esto es insuficiente por lo que se trabaja actualmente en identificación de alteraciones moleculares que permitan identificar subtipos que puedan establecer de manera más precisa el pronóstico del paciente. Este estudio preliminar buscó la estandarización del método de cuantificación en muestras prostáticas de FFPE de la expresión de los transcritos de posibles biomarcadores, como los oncogenes SPINK-1 y EZH2, el supresor tumoral NKX3.1, en conjunto con la determinación de la presencia/ausencia del gen de fusión TMPRSS2:ERG, ya que estos transcritos se encuentran involucrados en aparentes eventos excluyentes de la evolución natural del CaP, que apoyan la posibilidad de una clasificación molecular para esta enfermedad.Palabras clave: expresión génica, neoplasia intraepitelial prostática, neoplasias de próstata, progresión de la enfermedad, puntuación de Gleason. ABSTRACTAt present doesn't exist tool to differentiate patients with prostate cancer (PCa) of poor prognosis of those with indolent disease that only require a controlled monitoring of the disease. Because of the coexistence of different premalignant and malignant foci in CaP, the understanding of the carcinogenesis process requires a better understanding. Currently, the morphological heterogeneity in PCa is evaluated with Gleason score, which is closely related to the prognosis of the disease, but this is insufficient so it is currently to work on identifying molecular alterations to identify subtypes that can establish more precisely the patient's prognosis. This preliminary study aimed to standardization of the method of quantification in prostatic samples of FFPE of expression of transcripts of possible biomarkers, such as the oncogenes, SPINK-1 y EZH2, the tumour suppressor, NKX3.1, together with the determination of the presence/absence of gene fusion, TMPRSS2:ERG, being that these transcripts are involved in apparent exclusive events of the natural evolution of PCa, that support the possibility of a molecular classification for this disease.

show abstract

“…16,17 SPINK1 is also expressed in the prostate and its expression increases with high tumor grade. 18 Strongly increased SPINK1 expression is found in about 10% of all prostate cancers and this is associated with adverse prognosis. 19,20 In surgically resected patients, increased SPINK1 expression is inversely related to gene fusions involving erythroblastosis virus E26 transformation-specific (ETS) family of transcriptions factors.…”

mentioning

confidence: 99%

“…Nearly half of the patients with advanced prostate cancer have clearly elevated serum concentrations of SPINK1. 18 Thus, measurement of SPINK1 in serum may also be useful for identification of suitable patients and for monitoring of response to treatment.…”

mentioning

confidence: 99%

Role of the tumor-associated trypsin inhibitor SPINK1 in cancer development

Stenman¹

2011

Asian J Androl

Self Cite

View full text Add to dashboard Cite

Increased Expression of Tumor-Associated Trypsin Inhibitor, TATI, in Prostate Cancer and in Androgen-Independent 22Rv1 Cells

Cited by 74 publications

References 27 publications

Autocrine induction of invasion and metastasis by tumor-associated trypsin inhibitor in human colon cancer cells

Autocrine induction of invasion and metastasis by tumor-associated trypsin inhibitor in human colon cancer cells

Estandarización del protocolo para la detección de las fusiones TMPRSS2:ERG y de la expresión de los genes EZH2, SPINK-1 y NKX3.1 en cáncer de próstata (CaP)

Role of the tumor-associated trypsin inhibitor SPINK1 in cancer development

Contact Info

Product

Resources

About