Increasing http://www.selleckchem.com/products/17-AAG(Geldanamycin).html evidences indicate an important role of ISL 1 in the development of some cancers. However, whether ISL 1 has any functional effect on tumorigenesis and how ISL 1 is regulated during cancer development are yet not clear. In the present study, we investigate whether ISL 1 plays an oncogenic role in human tumors. We show that abnor mal high e pression of ISL 1 is significantly correlated with NHL and is specifically e hibited in 75% of human NHL samples we e amined. Aberrant ISL 1 is regulated by p STAT3 p c Jun ISL 1 transcription comple and potentiates NHL cells proliferation through up regulating c Myc e pression. Our findings reveal the feasibility of ISL 1 as a potential therapeutic target for NHL treatment.

Results ISL 1 is highly e pressed in 75% of human NHL samples In our pilot study, the specimens from different types of tumors were analyzed by immunohistochemical staining. The results showed a high e pression level of ISL 1 in diffuse large B cell lymphoma, compared with reactive lymph nodes. To e amine the pathological relevance of ISL 1 in human lymphoma development, we analyzed the e pression level and cellular distribution of ISL 1 in collected specimens and tissue microarrays by immunohistochemical staining. These tissue specimens included 23 normal lymph nodes and 211 lymphoma samples. The lymphoma specimens could be classified into two types 195 NHL and 16 Hodgkin lymph oma. As summarized in Table 1, ISL 1 e pression level is markedly elevated in 75% of 195 NHL samples.

Only 3 cases of normal lymph nodes e hibited moderate ISL 1 immunostaining, none of the 23 normal lymph nodes or 16 HL showed any strong positive staining for ISL 1. Figure 1A shows representative immunohistochemistry images of ISL 1 staining in human normal lymph node, HL and NHL. ISL 1 staining was predominantly detected in the nuclear of a series of NHL lymphoma cells and, to a much lesser e tent, in the normal lymph nodes and HL samples. Statistical analysis revealed that there was no significant difference in the e pression of ISL 1 between normal lymph nodes and HL samples, whereas, the positive staining of ISL 1 was significantly correlated with NHLs compared with that in normal lymph nodes. Meanwhile, we found a predominant e pression of ISL 1 in a variety of NHL cell lines. These data establish that ISL 1 e pression is highly elevated in the majority of NHLs and might be tightly linked to lymphomagenesis.

ISL 1 promotes proliferation of NHL cells in vitro and enhances enografted lymphoma development in vivo We have previously shown that ISL 1 promoted the pro liferation of adult pancreatic islets cells. We wonder whether up regulated ISL 1 in NHL plays a role in promot ing NHL cells proliferation GSK-3 and tumorigenesis. Therefore, Raji, Jurkat and Ly3 were electroporated with pcDNA3. 1 ISL1, or pLL3. 7 ISL1 siRNA plasmid to establish stable ISL 1 overe pressing or knockdown NHL cell lines.