Expression and localization of GLUT1 and GLUT12 in prostate carcinoma

Abstract

BACKGROUND Increased glucose consumption is a characteristic of malignant cells and in prostate carcinoma is associated with the proliferation of both androgen‐dependent and independent cells. Transport of polar glucose across the nonpolar membrane relies on glucose transporter proteins, known as GLUTs. Increased expression of GLUT1 is a characteristic of many malignant cells. The authors characterized and cloned the cDNA for a novel glucose transporter, GLUT12, which was identified initially in malignant breast epithelial cells. To the authors' knowledge, there have been no reports on the expression of glucose transporters in the human prostate or human prostate carcinoma cells. The authors evaluated GLUT1 and GLUT12 expression in human prostate carcinoma cells. METHODS Reverse transcription‐polymerase chain reaction was performed on total RNA extracted from cultured prostate carcinoma cells LNCaP, C4, C4‐2, and C4‐2B using primers to amplify GLUT1, GLUT12, or the housekeeping gene, 36B4. Total protein extracted from prostate carcinoma cell lines was assessed for GLUT12 protein by Western blot analysis. Cultured cell monolayers were incubated with antibodies to GLUT1 or GLUT12 and a peripheral Golgi protein, Golgi 58K, for detection by immunofluorescent confocal microscopy. Sections of benign prostatic hyperplasia and human prostate carcinoma were stained for immunohistochemical detection of GLUT1 and GLUT12. RESULTS GLUT1 and GLUT12 mRNA and protein were detected in all cell lines evaluated. Immunofluorescence staining demonstrated both GLUT1 and GLUT12 on the plasma membrane and in the cytoplasm in all cultured prostate carcinoma cell lines, with GLUT1 but not GLUT12 appearing to colocalize with the Golgi. Immunohistochemical staining of benign prostatic hyperplasia indicated expression of GLUT1 but not GLUT12. Malignant tissue stained for GLUT12 but was negative for GLUT1. CONCLUSIONS GLUT1 and GLUT12 are expressed in human prostate carcinoma cells. One possible rationale for the GLUT1 Golgi association is that it may supply glucose to the Golgi for byproduct incorporation into the prostatic secretory fluid. Further work will investigate the importance of glucose transport and GLUT1 and GLUT12 in prostate carcinoma cell growth. Cancer 2003;97:2035–42. © 2003 American Cancer Society. DOI 10.1002/cncr.11293

Cellular distribution of Glut‐1 and Glut‐5 in benign and malignant human prostate tissue

“…Our data indicated a very low level of expression of Glut‐1 in clinical specimens of CaP, which could explain, at least in part, the lack of effectiveness of FDG‐PET for imaging CaP. Our data support the study by Chandler et al [2003], which indicated that out of three clinical specimens of CaP analyzed, only one showed weak expression of Glut‐1. Our results, however, contrast with the analyzes reported by Effert et al [2004] and Steward et al [2008], which indicated that expression of Glut‐1 was higher in CaP than benign prostatic hyperplasia.…”

Cellular distribution of Glut‐1 and Glut‐5 in benign and malignant human prostate tissue

“…Our data indicated a very low level of expression of Glut‐1 in clinical specimens of CaP, which could explain, at least in part, the lack of effectiveness of FDG‐PET for imaging CaP. Our data support the study by Chandler et al [2003], which indicated that out of three clinical specimens of CaP analyzed, only one showed weak expression of Glut‐1. Our results, however, contrast with the analyzes reported by Effert et al [2004] and Steward et al [2008], which indicated that expression of Glut‐1 was higher in CaP than benign prostatic hyperplasia.…”

GLUT12 promotes prostate cancer cell growth and is regulated by androgens and CaMKK2 signaling

“…Hence, a potential oncogenic role for this transporter has been emerging. In agreement with the mRNA expression data listed in Table 1, immunohistochemical staining for GLUT12 revealed the transporter’s protein expression in malignant but not benign prostatic hyperplasia tissue (Chandler et al 2003). In estrogen receptor-positive (ER+) MCF-7 breast cancer cells, 24 h treatment with the steroid hormone estrogen was shown to increase GLUT12 protein but not mRNA levels, suggesting estrogen increased GLUT12 levels through promoting translation or protein stability (Macheda, et al 2005).…”

Organ-Specific Cancer Metabolism and Its Potential for Therapy

“…This is further in agreement with cell line studies, which show that the metastastic androgen-sensitive cell line LNCaP and the castration-resistant low-differentiation cell lines DU-145 and PC-3 are sensitive to glucose starvation [152] and that androgen signaling enhances the expression of glycolytic enzymes [161][162][163]. However, whether or not an increased expression of the glucose transporter 1 or other hexose transporters are causal for this phenotype is still a matter of debate, since histological data are inconclusive [164][165][166][167].…”

Cellular distribution of Glut‐1 and Glut‐5 in benign and malignant human prostate tissue

“…Our data indicated a very low level of expression of Glut‐1 in clinical specimens of CaP, which could explain, at least in part, the lack of effectiveness of FDG‐PET for imaging CaP. Our data support the study by Chandler et al [2003], which indicated that out of three clinical specimens of CaP analyzed, only one showed weak expression of Glut‐1. Our results, however, contrast with the analyzes reported by Effert et al [2004] and Steward et al [2008], which indicated that expression of Glut‐1 was higher in CaP than benign prostatic hyperplasia.…”

GLUT12 promotes prostate cancer cell growth and is regulated by androgens and CaMKK2 signaling

“…Hence, a potential oncogenic role for this transporter has been emerging. In agreement with the mRNA expression data listed in Table 1, immunohistochemical staining for GLUT12 revealed the transporter’s protein expression in malignant but not benign prostatic hyperplasia tissue (Chandler et al 2003). In estrogen receptor-positive (ER+) MCF-7 breast cancer cells, 24 h treatment with the steroid hormone estrogen was shown to increase GLUT12 protein but not mRNA levels, suggesting estrogen increased GLUT12 levels through promoting translation or protein stability (Macheda, et al 2005).…”

Organ-Specific Cancer Metabolism and Its Potential for Therapy

“…This is further in agreement with cell line studies, which show that the metastastic androgen-sensitive cell line LNCaP and the castration-resistant low-differentiation cell lines DU-145 and PC-3 are sensitive to glucose starvation [152] and that androgen signaling enhances the expression of glycolytic enzymes [161][162][163]. However, whether or not an increased expression of the glucose transporter 1 or other hexose transporters are causal for this phenotype is still a matter of debate, since histological data are inconclusive [164][165][166][167].…”

Cellular distribution of Glut‐1 and Glut‐5 in benign and malignant human prostate tissue

“…Our data indicated a very low level of expression of Glut‐1 in clinical specimens of CaP, which could explain, at least in part, the lack of effectiveness of FDG‐PET for imaging CaP. Our data support the study by Chandler et al [2003], which indicated that out of three clinical specimens of CaP analyzed, only one showed weak expression of Glut‐1. Our results, however, contrast with the analyzes reported by Effert et al [2004] and Steward et al [2008], which indicated that expression of Glut‐1 was higher in CaP than benign prostatic hyperplasia.…”

GLUT12 promotes prostate cancer cell growth and is regulated by androgens and CaMKK2 signaling

“…Hence, a potential oncogenic role for this transporter has been emerging. In agreement with the mRNA expression data listed in Table 1, immunohistochemical staining for GLUT12 revealed the transporter’s protein expression in malignant but not benign prostatic hyperplasia tissue (Chandler et al 2003). In estrogen receptor-positive (ER+) MCF-7 breast cancer cells, 24 h treatment with the steroid hormone estrogen was shown to increase GLUT12 protein but not mRNA levels, suggesting estrogen increased GLUT12 levels through promoting translation or protein stability (Macheda, et al 2005).…”

Organ-Specific Cancer Metabolism and Its Potential for Therapy

“…This is further in agreement with cell line studies, which show that the metastastic androgen-sensitive cell line LNCaP and the castration-resistant low-differentiation cell lines DU-145 and PC-3 are sensitive to glucose starvation [152] and that androgen signaling enhances the expression of glycolytic enzymes [161][162][163]. However, whether or not an increased expression of the glucose transporter 1 or other hexose transporters are causal for this phenotype is still a matter of debate, since histological data are inconclusive [164][165][166][167].…”