Expression of the cell death-inducing gene bax in carcinomas developed from the follicular cells of the thyroid gland.
The expression of apoptosis-regulating proteins, Bcl-2, Bax, Mcl-1, and Bcl-X, was evaluated by immunohistochemical methods in 39 cases of thyroid carcinomas. Normal thyroid tissues showed a consistent expression of Bcl-2 and Mcl-1 whereas Bax and Bcl-X proteins were essentially absent from most follicular thyroid cells. Bax expression was observed in all papillary carcinomas (n = 23) and in 8 of 10 follicular carcinomas. The intensity of Bcl-2 immunostaining was generally higher in follicular tumors (n = 10) than in papillary carcinomas (n = 21 of 23). However, in undifferentiated tumors, both Bax and Bcl-2 were weakly expressed. Mcl-1 protein expression was similar to that of Bax in papillary and follicular tumors, but was also frequently detectable in undifferentiated tumors. Bcl-X immunostaining was seen in all undifferentiated tumors (n = 6), in 22 of 23 papillary tumors, and in 5 of 10 follicular tumors. Our findings show that the regulation of bcl-2 family gene expression is different in normal thyroid tissue compared to that of its neoplastic counterpart and varies with the tumor subtype. In particular, unlike normal thyroid epithelium, the apoptosis-blocking gene bcl-X and the apoptosis-inducing gene bax are frequently expressed in thyroid carcinomas derived from the follicular cells. Thus, alterations in the expression of these bcl-2 family genes may contribute to the pathogenesis of thyroid carcinomas.
Branet
F
F
Service d'Endocrinologie, Centre Hospitalier Universitaire de Rangueil, Toulouse, France.
Brousset
P
P
Krajewski
S
S
Schlaifer
D
D
Selves
J
J
Reed
J C
JC
Caron
P
P
D018263:Adenocarcinoma, Follicular / Q000737:chemistry / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000737:chemistry / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D013964:Thyroid Neoplasms / Q000737:chemistry / Q000235:genetics*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein