Decreased expression of the human stem cell marker, Rex-1 (zfp-42), in renal cell carcinoma

Jay D. Raman, Nigel P. Mongan, Limin Liu, Satish K. Tickoo, David M. Nanus, Douglas S. Scherr, Lorraine J. Gudas

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Abstract

The Rex-1 (Zfp-42) gene encodes a zinc finger family transcription factor which is highly expressed in mouse and human embryonic stem cells. It is one of several gene markers used to identify human stem cells. While several organs are known to harbor adult human stem cells, the presence and distribution of stem cells in both the normal and neoplastic adult kidney remains largely unknown. In this study we evaluated Rex-1 mRNA and protein expression in normal and malignant kidney tissue specimens from human patients. Rex-1mRNA expression was determined using both reverse transcription and real-time PCR. REX1 protein expression was assessed by western analysis and immunohistochemistry, using an affinity-purified, polyclonal antibody to the REX1 protein. We found that 14 of 15 (93%) non-tumor renal parenchymal specimens demonstrated Rex-1mRNA, compared with 5 of 14 (36%) renal tumors (P=< 0.005). REX1 protein expression was detected in 21 of 23 (91%) non-tumor and in 7 of 19 (37%) tumor specimens (P= < 0.001). Furthermore, in six of these seven renal tumor specimens where REX1 protein expression was detected, the levels were at least 3-fold lower than those in adjacent, normal kidney tissue. There were no differences in Rex-1 mRNA or protein expression among the various histologic subtypes of renal tumors (clear cell carcinoma, papillary carcinoma, chromophobe carcinoma and oncocytoma). Immunohistochemical staining confirmed the absence of REX1 in three renal tumor specimens (two clear cell and one papillary carcinoma), while the REX1 protein was detected in a small percentage of proximal tubular cells in normal renal tissue. Immunohistochemical staining of another stem cell marker, OCT4, demonstrated a similar pattern of protein expression in a small percentage of normal renal proximal tubular cells. In summary, we were able to detect Rex-1 mRNA and protein expression in over 90% of normal renal parenchymal specimens and we observed a significant reduction in REX1 expression in renal tumor specimens of all histologic subtypes.

Original languageEnglish (US)
Pages (from-to)499-507
Number of pages9
JournalCarcinogenesis
Volume27
Issue number3
DOIs
StatePublished - Mar 1 2006

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Renal Cell Carcinoma
Stem Cells
Kidney
Proteins
Neoplasms
Papillary Carcinoma
Messenger RNA
Staining and Labeling
Oxyphilic Adenoma
Adult Stem Cells
Zinc Fingers
Genes
Reverse Transcription
Real-Time Polymerase Chain Reaction
Transcription Factors
Immunohistochemistry
Carcinoma
Antibodies

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Raman, J. D., Mongan, N. P., Liu, L., Tickoo, S. K., Nanus, D. M., Scherr, D. S., & Gudas, L. J. (2006). Decreased expression of the human stem cell marker, Rex-1 (zfp-42), in renal cell carcinoma. Carcinogenesis, 27(3), 499-507. https://doi.org/10.1093/carcin/bgi299
Raman, Jay D. ; Mongan, Nigel P. ; Liu, Limin ; Tickoo, Satish K. ; Nanus, David M. ; Scherr, Douglas S. ; Gudas, Lorraine J. / Decreased expression of the human stem cell marker, Rex-1 (zfp-42), in renal cell carcinoma. In: Carcinogenesis. 2006 ; Vol. 27, No. 3. pp. 499-507.
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abstract = "The Rex-1 (Zfp-42) gene encodes a zinc finger family transcription factor which is highly expressed in mouse and human embryonic stem cells. It is one of several gene markers used to identify human stem cells. While several organs are known to harbor adult human stem cells, the presence and distribution of stem cells in both the normal and neoplastic adult kidney remains largely unknown. In this study we evaluated Rex-1 mRNA and protein expression in normal and malignant kidney tissue specimens from human patients. Rex-1mRNA expression was determined using both reverse transcription and real-time PCR. REX1 protein expression was assessed by western analysis and immunohistochemistry, using an affinity-purified, polyclonal antibody to the REX1 protein. We found that 14 of 15 (93{\%}) non-tumor renal parenchymal specimens demonstrated Rex-1mRNA, compared with 5 of 14 (36{\%}) renal tumors (P=< 0.005). REX1 protein expression was detected in 21 of 23 (91{\%}) non-tumor and in 7 of 19 (37{\%}) tumor specimens (P= < 0.001). Furthermore, in six of these seven renal tumor specimens where REX1 protein expression was detected, the levels were at least 3-fold lower than those in adjacent, normal kidney tissue. There were no differences in Rex-1 mRNA or protein expression among the various histologic subtypes of renal tumors (clear cell carcinoma, papillary carcinoma, chromophobe carcinoma and oncocytoma). Immunohistochemical staining confirmed the absence of REX1 in three renal tumor specimens (two clear cell and one papillary carcinoma), while the REX1 protein was detected in a small percentage of proximal tubular cells in normal renal tissue. Immunohistochemical staining of another stem cell marker, OCT4, demonstrated a similar pattern of protein expression in a small percentage of normal renal proximal tubular cells. In summary, we were able to detect Rex-1 mRNA and protein expression in over 90{\%} of normal renal parenchymal specimens and we observed a significant reduction in REX1 expression in renal tumor specimens of all histologic subtypes.",
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Raman, JD, Mongan, NP, Liu, L, Tickoo, SK, Nanus, DM, Scherr, DS & Gudas, LJ 2006, 'Decreased expression of the human stem cell marker, Rex-1 (zfp-42), in renal cell carcinoma', Carcinogenesis, vol. 27, no. 3, pp. 499-507. https://doi.org/10.1093/carcin/bgi299

Decreased expression of the human stem cell marker, Rex-1 (zfp-42), in renal cell carcinoma. / Raman, Jay D.; Mongan, Nigel P.; Liu, Limin; Tickoo, Satish K.; Nanus, David M.; Scherr, Douglas S.; Gudas, Lorraine J.

In: Carcinogenesis, Vol. 27, No. 3, 01.03.2006, p. 499-507.

Research output: Contribution to journalArticle

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T1 - Decreased expression of the human stem cell marker, Rex-1 (zfp-42), in renal cell carcinoma

AU - Raman, Jay D.

AU - Mongan, Nigel P.

AU - Liu, Limin

AU - Tickoo, Satish K.

AU - Nanus, David M.

AU - Scherr, Douglas S.

AU - Gudas, Lorraine J.

PY - 2006/3/1

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N2 - The Rex-1 (Zfp-42) gene encodes a zinc finger family transcription factor which is highly expressed in mouse and human embryonic stem cells. It is one of several gene markers used to identify human stem cells. While several organs are known to harbor adult human stem cells, the presence and distribution of stem cells in both the normal and neoplastic adult kidney remains largely unknown. In this study we evaluated Rex-1 mRNA and protein expression in normal and malignant kidney tissue specimens from human patients. Rex-1mRNA expression was determined using both reverse transcription and real-time PCR. REX1 protein expression was assessed by western analysis and immunohistochemistry, using an affinity-purified, polyclonal antibody to the REX1 protein. We found that 14 of 15 (93%) non-tumor renal parenchymal specimens demonstrated Rex-1mRNA, compared with 5 of 14 (36%) renal tumors (P=< 0.005). REX1 protein expression was detected in 21 of 23 (91%) non-tumor and in 7 of 19 (37%) tumor specimens (P= < 0.001). Furthermore, in six of these seven renal tumor specimens where REX1 protein expression was detected, the levels were at least 3-fold lower than those in adjacent, normal kidney tissue. There were no differences in Rex-1 mRNA or protein expression among the various histologic subtypes of renal tumors (clear cell carcinoma, papillary carcinoma, chromophobe carcinoma and oncocytoma). Immunohistochemical staining confirmed the absence of REX1 in three renal tumor specimens (two clear cell and one papillary carcinoma), while the REX1 protein was detected in a small percentage of proximal tubular cells in normal renal tissue. Immunohistochemical staining of another stem cell marker, OCT4, demonstrated a similar pattern of protein expression in a small percentage of normal renal proximal tubular cells. In summary, we were able to detect Rex-1 mRNA and protein expression in over 90% of normal renal parenchymal specimens and we observed a significant reduction in REX1 expression in renal tumor specimens of all histologic subtypes.

AB - The Rex-1 (Zfp-42) gene encodes a zinc finger family transcription factor which is highly expressed in mouse and human embryonic stem cells. It is one of several gene markers used to identify human stem cells. While several organs are known to harbor adult human stem cells, the presence and distribution of stem cells in both the normal and neoplastic adult kidney remains largely unknown. In this study we evaluated Rex-1 mRNA and protein expression in normal and malignant kidney tissue specimens from human patients. Rex-1mRNA expression was determined using both reverse transcription and real-time PCR. REX1 protein expression was assessed by western analysis and immunohistochemistry, using an affinity-purified, polyclonal antibody to the REX1 protein. We found that 14 of 15 (93%) non-tumor renal parenchymal specimens demonstrated Rex-1mRNA, compared with 5 of 14 (36%) renal tumors (P=< 0.005). REX1 protein expression was detected in 21 of 23 (91%) non-tumor and in 7 of 19 (37%) tumor specimens (P= < 0.001). Furthermore, in six of these seven renal tumor specimens where REX1 protein expression was detected, the levels were at least 3-fold lower than those in adjacent, normal kidney tissue. There were no differences in Rex-1 mRNA or protein expression among the various histologic subtypes of renal tumors (clear cell carcinoma, papillary carcinoma, chromophobe carcinoma and oncocytoma). Immunohistochemical staining confirmed the absence of REX1 in three renal tumor specimens (two clear cell and one papillary carcinoma), while the REX1 protein was detected in a small percentage of proximal tubular cells in normal renal tissue. Immunohistochemical staining of another stem cell marker, OCT4, demonstrated a similar pattern of protein expression in a small percentage of normal renal proximal tubular cells. In summary, we were able to detect Rex-1 mRNA and protein expression in over 90% of normal renal parenchymal specimens and we observed a significant reduction in REX1 expression in renal tumor specimens of all histologic subtypes.

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