nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma

Abstract

Background: The discovery that genetic alterations in oncogenes and tumour suppressor genes accompany tumour formation in many human tumours has encouraged the search for genes that promote or suppress tumour spread and metastasis; nm23 is a promising candidate for a metastasis suppressing gene. Aims: To evaluate whether expression of nm23-H1 protein or loss of heterozygosity (LOH) of the nm23-H1 gene is associated with colon cancer progression. Materials/Methods: Paraffin wax embedded tissue sections were analysed immunohistochemically. DNA isolated from normal and tumour tissue was used for LOH analysis using a variable nucleotide tandem repeat (VNTR) marker located in the untranslated 59 region of the nm23-H1 gene. RNA isolated from tumour and normal tissue was used for ''real time'' RT-PCR. Results: Of 102 adenocarcinomas examined, 58.8% stained weakly for nm23-H1 protein. There was a negative correlation between nm23-H1 positivity and tumour histological grade. In VNTR analysis, 70.2% of patients were informative and 27.4% of tumours had nm23-H1 LOH. There was a positive correlation between nm23-H1 LOH and both tumour histological grade and Dukes's stage. Expression of nm23-H1 mRNA was increased in 22 of 30 colon tumours compared with normal tissue. No significant correlation was found between nm23-H1 mRNA expression and histological grade or Dukes's stage of tumours. Conclusions: These findings suggest that nm23-H1 protein expression in early stages may have a role in suppressing metastasis in sporadic colon cancer, whereas at a later stage both reduced nm23-H1 protein expression and LOH of the nm23-H1 gene may play role in colon cancer progression and metastasis.

Immunohistochemical localization of the NM23 protein in salivary gland neoplasms with distinct biological behavior

“…In the present work, less intense immunostaining was obtained with the NM301 clone, but similar histo-morphological distribution of NM23-positive cells was observed using both antibodies, resulting in a strong statistical correlation between the immunostaining indices of these two antibodies. Similar result was also found in colorectal carcinomas [18]. Thus, we believed that the distribution of NM23 protein in the SGN of this study is representative and the data of this study are reliable.…”

TNFα gene/protein in tumorigenesis of sporadic colon adenocarcinoma

“…Results are shown as ΔCt values, which is the difference in cycle number required to raise the amount of PCR product above threshold. ΔCt is therefore inversely proportional to the amounts of mRNA (Kapitanović et al, 2004).…”

STRAD in Peutz-Jeghers syndrome and sporadic cancers

“…36 At chromosomal location 17q21.3, the metastasis suppressor NM23-H1 has been suggested to play a role in colon cancer progression and metastasis. 37 However, LOH of NM23-H1 was found in only 14% of gastric carcinomas, indicating that inactivation is not essential in gastric cancer. 38 Based on our results, STRAD does not seem to be essential for tumour formation in the sporadic tumour types studied.…”