Determination and characterization of hexokinase in thyroid cancer and benign neoplasms

Abstract

Hexokinase (ADP: D‐hexose‐6‐phosphotransferase, EC 2.7.1.1) was studied in human thyroid carcinomas (n = 11), follicular adenomas (n = 32), and normal thyroid tissue (n = 21). The specific activity was significantly increased in carcinoma (0.163 ± 0.083 U/mg protein) compared with normal tissue (0.030 ± 0.010 U/mg protein) (P < 0.001). Specific activities of follicular adenomas are rather heterogeneous, but when subdivided into three groups according to histopathologic criteria, a significant difference was found between follicular adenomas group I and II and follicular adenomas group III. A lesser cellular differentiation of adenomas is indicated by the lower degree or even absence of colloid production and follicle formation. A higher proliferation rate may be assumed on the grounds of the irregularities in outline, the often defective pseudocapsule, and signs of compression of the surrounding tissue. The highest specific activity in adenomas was found in the group with the highest proliferative activity, i.e., group III, whereas the lowest specific activities were found in adenomas with the lowest grade of proliferation, i.e., group I; the former was comparable with values found in carcinomas and the latter was comparable with values found in normal thyroid tissue. An interesting difference was found when the compartmentation of hexokinase was compared in carcinomas of different degree of differentiation. In papillary carcinomas a significantly lower proportion of hexokinase (HK) is present in the cytosol in comparison to follicular and undifferentiated carcinomas. In carcinomas more HK II and less HK I was found in comparison with normal thyroid tissue. In contrast hexokinase isozyme composition and compartmentation in adenomas were not different from normal thyroid tissue.

Combined RNA Interference of Hexokinase II and 131I-Sodium Iodide Symporter Gene Therapy for Anaplastic Thyroid Carcinoma

“…Therefore, the additional use of other therapeutic strategies, such as chemotherapy or external radiotherapy, is necessary to treat cancer and achieve therapeutic goals without severe adverse effects related to the radioiodine therapy. ATC has been characterized and classified as distinct from differentiated thyroid carcinoma by a higher percentage of HKII in the mitochondrial fraction (30). In particular, mitochondrion-bound HKII is correlated with high glycolytic rates in tumors, and inactivation of this enzyme can retard tumor growth by inhibiting glucose metabolism, which is enhanced in most tumor cells (31,32).…”

Endothelin‐1 stimulates the translocation and upregulation of both glucose transporter and hexokinase in astrocytes: relationship with gap junctional communication

“…1994) and type II hexokinase (Singh et al . 1978; Verhagen et al . 1985; Sebastian and Kenkare 1998; for a review see Mathupala et al .…”

Increased levels of cyclins D1 and D3 after inhibition of gap junctional communication in astrocytes

“…1994) and type II hexokinase, the first enzyme involved in glucose metabolism (Singh et al . 1978; Verhagen et al . 1985; Sebastian and Kenkare 1998; for review see Mathupala et al .…”