The expression of low molecular weight protein tyrosine phosphatase is up‐regulated in 1,2‐dimethylhydrazine‐induced colon tumours in rats

Abstract

Recent studies have assessed the role of low molecular weight protein tyrosine phosphatase (LMW-PTP) in cell transformation and tumour onset and progression, observing a significant increase in the expression of LMW-PTP mRNA and protein in human breast, colon, bladder and kidney tumour samples. Moreover, its enhanced expression is generally prognostic of a more aggressive cancer. To better understand the role of this protein during colon carcinogenesis and to study whether its overexpression is also observed in earlier phases of carcinogenesis, we studied its expression in colon tumours, induced in rats by treatment with 1,2-dimethylhydrazine (DMH), an animal model that resemble the sequential formation of histopathological lesions of spontaneous carcinogenesis in humans. The results show a significant increase in LMW-PTP expression in adenocarcinomas, suggesting that this phenomenon is associated with the onset of malignancy. Moreover a significant overexpression of LMW-PTP transcript is associated with tumours originating in the proximal (right) part of the colon, confirming an observation already reported for human colon cancer. ' 2007 Wiley-Liss, Inc.

Morin‐dependent inhibition of low molecular weight protein tyrosine phosphatase (LMW‐PTP) restores sensitivity to apoptosis during colon carcinogenesis: Studies in vitro and in vivo, in an Apc‐driven model of colon cancer

“…Accordingly, in the present paper, the over‐expression of LMW‐PTP was observed in the NM of rats aged 8 weeks, when no tumors and only a few microscopic lesions are present in the colon mucosa . We also show that Pirc colon tumors over‐express LMW‐PTP when compared to their corresponding NM, in agreement with previous data with colon tumors in rodents . Taken together these data suggest that Apc mutated cells express high LMW‐PTP levels and that LMW‐PTP levels increase in the process of colon carcinogenesis.…”

“…LMW‐PTP over‐expression has been reported so far in several types of cancer, including CRC, as we showed in clinical colon cancer samples and in rodent DMH‐induced colon cancers . Although Hoekstra et al reported a step‐wise increase in LMW‐PTP expression in different stages of colon dysplasia, there were no data on the over‐expression of LMW‐PTP at such an early stage of carcinogenesis, as the NM of Pirc rats can be considered .…”

From immune response to cancer: a spot on the low molecular weight protein tyrosine phosphatase

“…LMWPTP expression is upregulated in various human cancers [32,55] and its biological roles may be of interest to understand cancer biology and the establishment of new cancer therapy strategies. The list of cancer relevant molecules apparently regulated by LMWPTP is growing and now includes the PDGFR [56], janus kinase 2 (JAK2) [57], signal transducer and activator of transcription 5 (STAT5) [58,59], Focal adhesion kinase (FAK) [35], Ephrin A2 receptor (Eph A2) [60], insulin receptor (IR) [61,51] and b-Catenin [62].…”

“…Such cellular behavior is a wellknown hallmark of invasive carcinoma. Therefore, high levels of LMWPTP are considered tumoral markers for aggressiveness and unfavorable prognosis [32,55].…”

Prostate Cancer Dephosphorylation Atlas

“…Taddei et al (2006) observed that, at least in part, the antitumoral activity of Aplidin could be due to the direct oxidation and inactivation of LMWPTP. Marzocchini et al (2008) reported that the treatment of rats with 1,2-dimethylhydrazine provoked a significant increase in LMWPTP expression in adenocarcinomas, suggesting that this phenomenon is associated with the onset of malignancy.…”