HU proteins belong to the nucleoid-associated proteins (NAPs) that are involved in vital processes such as DNA compaction and reparation, gene transcription etc. No data are available on the structures of HU proteins from mycoplasmas. To this end, the HU protein from the parasitic mycoplasma Spiroplasma melliferum KC3 was cloned, overexpressed in Escherichia coli and purified to homogeneity. Prismatic crystals of the protein were obtained by the vapour-diffusion technique at 4°C. The crystals diffracted to 1.36 Å resolution (the best resolution ever obtained for a HU protein). The diffraction data were indexed in space group C2 and the structure of the protein was solved by the molecular-replacement method with one monomer per asymmetric unit.
Most previous studies on RET and p53 proteins have focused on thyroid papillary carcinoma. We investigated the role of RET and p53 protein expressions using immunohistochemistry on 52 cases of thyroid follicular adenomas and studied the follow-up records of these patients. The range of follow-up period was 3 to 14 years. The patients were between 15 and 71 years of age with a median age of 34.5 years. There were 46 females and 6 males. Except for 3 cases, all patients were Malays. The minimum volume of the tumour was 1000 mm3 and the maximum was 512,000 mm3 with a median of 270,000 mm3. Eleven (21.2%) cases showed RET expression. RET expression was not statistically significant when cross-tabulated against sex (p = 0.322), ethnicity (p = 0.518), age (p = 0.466) and symptom duration (p = 0.144). Six (11.5%) of 52 cases showed p53 immunopositivity. p53 expressions were also not significantly correlated to the clinical parameters above. There was no correlation between RET and p53 protein expressions. The only statistically significant finding was the association of tumour volume with duration of symptoms (p = 0.05). All patients are alive at the time of writing. 3 had recurrent goitre, 2 of these were diagnosed as colloid goitre while the third was a follicular lesion. One patient suffered from depression requiring anti-depressant treatment. In conclusion, unlike papillary carcinoma in which the roles of ret and p53 oncogenes are known, their roles in influencing the behaviour of follicular adenoma has not been ascertained.
Human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, is strongly associated with telomerase activity implicated in cellular immortalization and tumorigenesis. In situ detection of hTERT will aid in determining the localization of telomerase positive cells. The aim of this study was to detect hTERT protein expression in multistep oral carcinogenesis using paraffin embedded tissue samples, and to study the relationship of hTERT expression with different histological stages in oral carcinogenesis. Normal (n = 4), hyperplastic (n = 4), dysplastic (n = 4) and neoplastic (n = 10) oral epithelia representing different histological stages in oral carcinogenesis were included in the study. hTERT protein detection was done by immunohistochemistry (IHC) technique. Nuclear staining intensities were noted and the hTERT-labelling index was determined. Dysplastic and neoplastic oral epithelia showed an increased percentage of hTERT positive cells (Grade 4: > 50% positive staining nuclei) with intense staining in the basal, parabasal and superficial layers of the epithelia, unlike normal oral mucosa which showed intense staining only in the basal and parabasal cell layers, which are the normal proliferative progenitor compartments. hTERT protein expression was elevated with the corresponding advancement of the histological stages of oral carcinogenesis, from normal to hyperplasia to dysplasia to carcinoma. There seems to be an upregulation of hTERT protein expression during the progression of oral cancer, therefore, this may indicate the feasibility of IHC detection of hTERT protein in oral carcinogenesis as a potential diagnostic or prognostic marker.
miR-1 and miR-133 are clustered on the same chromosomal loci and are transcribed together as a single transcript that is positively regulated by ecotropic virus integration site-1 (EVI1). Previously, we described how miR-133 has anti-tumorigenic potential through repression of EVI1 expression. It has also been reported that miR-1 is oncogenic in the case of acute myeloid leukemia (AML). Here, we show that expression of miR-1 and miR-133, which have distinct functions, is differentially regulated between AML cell lines. Interestingly, the expression of miR-1 and EVI1, which binds to the promoter of the miR-1/miR-133 cluster, is correlative. The expression levels of TDP-43, an RNA-binding protein that has been reported to increase the expression, but inhibits the activity, of miR-1, were not correlated with expression levels of miR-1 in AML cells. Taken together, our observations raise the possibility that the balance of polycistronic miRNAs is regulated post-transcriptionally in a hierarchical manner possibly involving EVI1, suggesting that the deregulation of this balance may play some role in AML cells with high EVI1 expression.
Malignant transformation from normal colonic mucosa to carcinomas may be accelerated by genetic loss or inactivation of genes of the DNA mismatch repair system. The aim of the study was to determine the local incidence and pattern of immunohistochemical expression of mismatch repair proteins namely: hMLH1, hMSH2 and hMSH6 in a series of colorectal carcinomas (CRCs) and correlate this to their clinical and pathological features. Forty-three out of 298 cases of CRCs (14.4%) showed abnormal staining pattern for mismatch repair proteins with a majority (65.1%) showing single hMLH1 loss. Tumours with mismatch repair defect (MMR-d) were frequently found at the right side of colon (p<0.001), poorly differentiated carcinomas (p<0.001), produced more mucin (p=0.007), exophytic growth (p=0.007) and were bigger (p=0.002) than tumours with no mismatch repair defect. Immunohistochemical stains for mismatch repair proteins could be done in local laboratories on these selected cases before referring for the expensive molecular test.