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Identification of Metastasis Associated Antigen 1 (MTA1) by Serological Screening of Prostate Cancer cDNA Libraries.

Geng L, Deepak P A, Aija L, Fuming C, Amanda M, Robert C R, Stephanie E B M - Open Biochem J (2008)

Bottom Line: Fifty five genes were isolated, including 46 known genes and 9 previously uncharacterised genes.Among the known genes, a metastasis-associated gene, MTA1, previously identified by differential cDNA hybridisation, was preferentially expressed in a panel of malignant tissues compared with normal tissues, as analysed by reverse transcriptase-polymerase chain reaction (RT-PCR).Based on these findings and previous reports on the literature on this gene, MTA-1 can be considered not only as a "biomarker" of aggressive disease but also as a potential therapeutic target.

View Article: PubMed Central - PubMed

Affiliation: School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK.

ABSTRACT
Over the past 10 years the serological analysis of recombinant cDNA expression libraries (SEREX) has proved to be an effective method for the identification of tumour antigens. In the present study, two prostate cancer libraries were constructed and screened using autologous sera. Fifty five genes were isolated, including 46 known genes and 9 previously uncharacterised genes. Among the known genes, a metastasis-associated gene, MTA1, previously identified by differential cDNA hybridisation, was preferentially expressed in a panel of malignant tissues compared with normal tissues, as analysed by reverse transcriptase-polymerase chain reaction (RT-PCR). MTA1 transcripts were observed to be over-expressed in normal human testes as well as various cancer tissues when compared to the panel of normal tissues. MTA1 antigen reacted with 2 of 13 allogeneic prostate cancer patient sera tested, but no sera reactivity was observed to any of the normal adult sera tested. Furthermore, a similar distribution and expression level of MTA-1 was observed in murine tissues and cancer cell lines. Based on these findings and previous reports on the literature on this gene, MTA-1 can be considered not only as a "biomarker" of aggressive disease but also as a potential therapeutic target.

No MeSH data available.


Related in: MedlinePlus

(A) Expression of MTA1 in normal human tissues analysed by RT-PCR. Cycling conditions were optimized so that the RT-PCR products were analyzed when amplification is within the linear phase. Lanes 1-9 from left to right, normal brain, kidney, heart, liver, lung, PBMC, testis, negative control and DNA ladder. (B) Tissue distribution of MTA1 transcript in malignant tissues and cell lines was analysed by RT-PCR. Lanes 1-4: prostate cancer tissues; lanes 5-7: prostate cancer cell lines (lane 5: DU-145; lane 6: LNCaP; lane 7: PC3); lanes 8-11: renal cancer; lanes 12-16: gastric cancer. Amplification of GAPDH was also performed in parallel as a control in all samples. (C) Agarose gel electrophoresis of mGAPDH and mMTA1 following RT- PCR from murine tumour cell lines and tissues. Lanes 1-10 from left to right, CT26, A20, RENCA, CMT, B16, liver, lung, muscle, spleen, kidney.
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Figure 1: (A) Expression of MTA1 in normal human tissues analysed by RT-PCR. Cycling conditions were optimized so that the RT-PCR products were analyzed when amplification is within the linear phase. Lanes 1-9 from left to right, normal brain, kidney, heart, liver, lung, PBMC, testis, negative control and DNA ladder. (B) Tissue distribution of MTA1 transcript in malignant tissues and cell lines was analysed by RT-PCR. Lanes 1-4: prostate cancer tissues; lanes 5-7: prostate cancer cell lines (lane 5: DU-145; lane 6: LNCaP; lane 7: PC3); lanes 8-11: renal cancer; lanes 12-16: gastric cancer. Amplification of GAPDH was also performed in parallel as a control in all samples. (C) Agarose gel electrophoresis of mGAPDH and mMTA1 following RT- PCR from murine tumour cell lines and tissues. Lanes 1-10 from left to right, CT26, A20, RENCA, CMT, B16, liver, lung, muscle, spleen, kidney.

Mentions: The expression pattern of MTA1 transcripts in a panel of normal human tissues, matched human non-tumour and tumour tissues, human prostate cancer tissues and cell lines was analysed by RT-PCR. Weak expression of MTA1 transcript was detected in normal human tissues except testis, where MTA1 was highly expressed (Fig. 1A). Human head and neck tumours and oesophageal cancer tissues expressed higher levels of MTA1 transcripts than matched non-tumour tissues (data not shown). MTA1 mRNA is highly expressed in human prostate cancer cell lines and a significant number of prostate, renal and stomach cancer tissues (Fig. 1B). We further analysed the expression of MTA1 in murine tissues and tumour cell lines since MTA1 is highly conserved in humans and mouse demonstrating 96% similarity at the protein level. MTA1 was found to be over-expressed in all murine tumour cell lines as compared to normal tissues, except the testis (Fig. 1C), which showed a similar level of expression to tumour tissues (data not shown). In comparison, all the normal tissues examined expressed MTA1 at very low levels (Fig. 1C). Interestingly, we found that MTA1 was expressed at low levels in muscle tissue compared to other tissues, which contradict previously published work where no MTA1 expression was found [14].


Identification of Metastasis Associated Antigen 1 (MTA1) by Serological Screening of Prostate Cancer cDNA Libraries.

Geng L, Deepak P A, Aija L, Fuming C, Amanda M, Robert C R, Stephanie E B M - Open Biochem J (2008)

(A) Expression of MTA1 in normal human tissues analysed by RT-PCR. Cycling conditions were optimized so that the RT-PCR products were analyzed when amplification is within the linear phase. Lanes 1-9 from left to right, normal brain, kidney, heart, liver, lung, PBMC, testis, negative control and DNA ladder. (B) Tissue distribution of MTA1 transcript in malignant tissues and cell lines was analysed by RT-PCR. Lanes 1-4: prostate cancer tissues; lanes 5-7: prostate cancer cell lines (lane 5: DU-145; lane 6: LNCaP; lane 7: PC3); lanes 8-11: renal cancer; lanes 12-16: gastric cancer. Amplification of GAPDH was also performed in parallel as a control in all samples. (C) Agarose gel electrophoresis of mGAPDH and mMTA1 following RT- PCR from murine tumour cell lines and tissues. Lanes 1-10 from left to right, CT26, A20, RENCA, CMT, B16, liver, lung, muscle, spleen, kidney.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2570555&req=5

Figure 1: (A) Expression of MTA1 in normal human tissues analysed by RT-PCR. Cycling conditions were optimized so that the RT-PCR products were analyzed when amplification is within the linear phase. Lanes 1-9 from left to right, normal brain, kidney, heart, liver, lung, PBMC, testis, negative control and DNA ladder. (B) Tissue distribution of MTA1 transcript in malignant tissues and cell lines was analysed by RT-PCR. Lanes 1-4: prostate cancer tissues; lanes 5-7: prostate cancer cell lines (lane 5: DU-145; lane 6: LNCaP; lane 7: PC3); lanes 8-11: renal cancer; lanes 12-16: gastric cancer. Amplification of GAPDH was also performed in parallel as a control in all samples. (C) Agarose gel electrophoresis of mGAPDH and mMTA1 following RT- PCR from murine tumour cell lines and tissues. Lanes 1-10 from left to right, CT26, A20, RENCA, CMT, B16, liver, lung, muscle, spleen, kidney.
Mentions: The expression pattern of MTA1 transcripts in a panel of normal human tissues, matched human non-tumour and tumour tissues, human prostate cancer tissues and cell lines was analysed by RT-PCR. Weak expression of MTA1 transcript was detected in normal human tissues except testis, where MTA1 was highly expressed (Fig. 1A). Human head and neck tumours and oesophageal cancer tissues expressed higher levels of MTA1 transcripts than matched non-tumour tissues (data not shown). MTA1 mRNA is highly expressed in human prostate cancer cell lines and a significant number of prostate, renal and stomach cancer tissues (Fig. 1B). We further analysed the expression of MTA1 in murine tissues and tumour cell lines since MTA1 is highly conserved in humans and mouse demonstrating 96% similarity at the protein level. MTA1 was found to be over-expressed in all murine tumour cell lines as compared to normal tissues, except the testis (Fig. 1C), which showed a similar level of expression to tumour tissues (data not shown). In comparison, all the normal tissues examined expressed MTA1 at very low levels (Fig. 1C). Interestingly, we found that MTA1 was expressed at low levels in muscle tissue compared to other tissues, which contradict previously published work where no MTA1 expression was found [14].

Bottom Line: Fifty five genes were isolated, including 46 known genes and 9 previously uncharacterised genes.Among the known genes, a metastasis-associated gene, MTA1, previously identified by differential cDNA hybridisation, was preferentially expressed in a panel of malignant tissues compared with normal tissues, as analysed by reverse transcriptase-polymerase chain reaction (RT-PCR).Based on these findings and previous reports on the literature on this gene, MTA-1 can be considered not only as a "biomarker" of aggressive disease but also as a potential therapeutic target.

View Article: PubMed Central - PubMed

Affiliation: School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK.

ABSTRACT
Over the past 10 years the serological analysis of recombinant cDNA expression libraries (SEREX) has proved to be an effective method for the identification of tumour antigens. In the present study, two prostate cancer libraries were constructed and screened using autologous sera. Fifty five genes were isolated, including 46 known genes and 9 previously uncharacterised genes. Among the known genes, a metastasis-associated gene, MTA1, previously identified by differential cDNA hybridisation, was preferentially expressed in a panel of malignant tissues compared with normal tissues, as analysed by reverse transcriptase-polymerase chain reaction (RT-PCR). MTA1 transcripts were observed to be over-expressed in normal human testes as well as various cancer tissues when compared to the panel of normal tissues. MTA1 antigen reacted with 2 of 13 allogeneic prostate cancer patient sera tested, but no sera reactivity was observed to any of the normal adult sera tested. Furthermore, a similar distribution and expression level of MTA-1 was observed in murine tissues and cancer cell lines. Based on these findings and previous reports on the literature on this gene, MTA-1 can be considered not only as a "biomarker" of aggressive disease but also as a potential therapeutic target.

No MeSH data available.


Related in: MedlinePlus