We have explored the mechanism of estrogen-induced growth in human uterine leiomyomas from the aspect of sex hormone-binding globulin (SHBG) exon VII splicing variant mRNA expression using the reverse transcription-polymerase chain reaction-Southern blot and DNA sequencing analyses. The results were obtained by analysis of the missing base pairs corresponding to the entire exon VII, which are considered to encode a portion of the steroid-binding site. This absence replaces 118 amino acids from the carboxy-terminus of SHBG with nine different amino acid residues due to the formation of a new stop codon at residue 334. The ratio of the SHBG variant to its wild-type mRNA levels in uterine leiomyomas was reduced, compared with that in the corresponding myometria in individual cases, while the SHBG wild-type and variant mRNA levels showed no significant difference during the menstrual phase. These studies demonstrate coexpression of SHBG exon VII splicing variant mRNA with its wild-type in human uterine myometria and leiomyomas. The reduced expression of the SHBG variant to wild-type mRNA levels in leiomyoma might be involved in the intracellular estrogen-predominant milieu, plausibly assisting in the development and growth of the leiomyoma.

Adult↗

PubMedDate not supplied

Expression of cell-cycle-regulating transcription factor E2F-1 in colorectal carcinomas.

The expression of E2F-1 in human colorectal carcinomas was examined immunohistochemically, and the correlation of E2F-1 expression with clinicopathological findings and with the expression of p27(Kip1) was analyzed to elucidate the role of E2F-1 in the development and progression of colorectal carcinomas. In nonneoplastic mucosa, a small number of epithelial cells in the proliferative zone were weakly positive for E2F-1. Weak expression of E2F-1 was detected in many adenoma cells. Most of the colorectal carcinomas expressed E2F-1 at various levels, and strong expression of E2F-1 was detected in 56% (49/88) of the cases. There was no correlation between the expression of E2F-1 and any clinicopathological parameters such as tumor stage, depth of tumor invasion and lymph node metastasis. Reduced expression of p27(Kip1) was confirmed to be significantly correlated with deep tumor invasion and presence of metastasis. No correlation was evident between overexpression of E2F-1 and reduced p27(Kip1) expression.

Adenocarcinoma↗

PubMedDate not supplied

Levels of corticosteroid-binding globulin mRNA in human ovarian cancers.

To understand the role of corticosteroid-binding globulin (CBG) in the intracellular steroidal actions in human ovarian cancers, the level of CBG mRNA expression was evaluated in normal ovarian tissues and in ovarian cancers using competitive reverse transcription-polymerase chain reaction-Southern blot analysis. The expression of CBG mRNA was detected in all normal ovaries and ovarian cancers analyzed. There were no significant differences in the mean CBG mRNA levels between normal ovaries and ovarian cancers. The expression in normal ovaries was significantly higher (p < 0.01) in the premenopause than in the postmenopause. A high expression of CBG mRNA was observed in 11 out of 29 cases (38%) of ovarian cancer in comparison with normal ovaries. There was no difference in the expression among the histological classifications or clinical stages of ovarian cancers. These data suggest that human normal ovaries and ovarian cancers might synthesize CBG intracellularly, ovarian cancers might conserve a progesterone-associated property via CBG, and the regulation of intracelluar CBG expression might be changed in some cancers.

Adult↗

PubMedDate not supplied

Expression of size-polymorphic androgen receptor gene in uterine leiomyoma according to the number of cytosine, adenine, and guanine repeats in androgen receptor alleles.

The amino terminus region of the androgen receptor (AR) gene in the X chromosome involves the cytosine, adenine, and guanine (CAG) repeats. Random X chromosome inactivation with AR alleles in individual cells occurs in females. Therefore, probably either paternal or maternal single dominant polymorphic AR mRNA must be expressed in neoplastic tissue originating from monoclone. This prompted us to determine the deviated numbers of CAG repeats in AR mRNA to understand the clonality of uterine leiomyoma. A solitary node of leiomyoma was macroscopically found in 7 cases, and multiple nodes were found in another 23 cases. Homozygous CAG repeats (22.0 +/- 2.3) in AR alleles were found in 5 of 30 cases, and either a large or small size of AR mRNA expression, were found in individual nodes of uterine leiomyoma, although paternal and maternal AR mRNAs from normal uterine myometrium were consistently expressed as AR alleles. There was no significant specificity in activated AR alleles related to CAG numbers in individual nodes. Therefore, an individual node of uterine leiomyoma might be formed from an independent monoclonal uterine leiomyoma cell.

Adenine↗

PubMedDate not supplied

Leukemia and other malignancies among GH users.

The number of reported cases of leukemia developing in growth hormone (GH) users worldwide has reached 31. Twelve Japanese cases are briefly reviewed; five each of AML and ALL, and one each of CML and malignant histiocytosis. The underlying diseases of these patients consisted of 8 idiopathic disease, 3 tumors and one Fanconi's anemia. Leukemia occurred during GH treatment in 9 cases and after cessation of GH in 3. The longest interval from the cessation of GH therapy was 10 years. GH administration from a younger age tended to be linked to myeloid type. Risk factors and possible mechanisms of leukemogenesis by growth hormone are discussed, and proposals for the future have been made by the Foundation for Growth Science in Japan.

Acute Disease↗

PubMedDate not supplied

Expression of p27Kip1, cyclin E and E2F-1 in primary and metastatic tumors of gastric carcinoma.

The cell cycle is controlled by positive and negative regulators. Gene abnormalities and aberrant expressions of various cyclins/CDKs and CDK inhibitors may play a pivotal role in stomach carcinogenesis. To clarify the role of cyclin E, CDK inhibitor p27Kip1 and their target molecule, E2F-1 in tumor metastasis, we examined immunohistochemically the expression of cyclin E, p27Kip1 and E2F-1 in 23 gastric carcinomas and metastatic tumors of the lymph node. Most of gastric carcinomas with lymph node metastasis showed reduced p27Kip1 expression. p27Kip1 was negative in 39% (9/23) of primary tumors, while it was so in 52% (12/23) of lymph node metastases. By comparison of p27Kip1 expression in primary and metastatic tumors in individual cases, metastatic tumor cells in the lymph nodes were expressed at weaker levels than in those in primary tumors in 43% (10/23) of the cases. On the other hand, over 70% (17/23) and 50% (12/23) of the cases expressed cyclin E and E2F-1 at nearly the same levels in both primary tumor and lymph node metastasis, respectively. These results suggest that tumor cells with reduced p27Kip1 expression may selectively metastasize to lymph node or distant organs.

Carrier Proteins↗

PubMedDate not supplied

Immunohistochemical expressions of estrogen and progesterone receptors in human epididymis at different ages--a preliminary study.

OBJECTIVE: To explore the biological significance of sex steroidal actions in human epididymis at various stages. PATIENTS AND METHODS: Human epididymides were obtained from 20 males aged from 2 days to 81 years at autopsy. Immunohistochemical staining for estrogen receptor (ER) and progesterone receptor (PR) was conducted using formalin-fixed paraffin-embedded sections of epididymides, by the avidinbiotin-peroxidase complex method. RESULTS: Positive immunohistochemical staining of ER was detected in the nucleus of epididymal epithelia in 14- to 64-year-old men, while in males aged from neonatal to 12 years, and over 65 years, ER was not detected in epididymides. On the other hand, PR was not detected in epididymis in any cases. CONCLUSION: Estrogen might contribute to reproductive epididymal functions after puberty and during maturity via estrogen-ER cascades.

Adolescent↗