Expression and alternative splicing pattern of human telomerase reverse transcriptase in human lung cancer cells.

Telomerase activity is generally considered to be necessary for cancer cells to avoid senescence. The expression of human telomerase reverse transcriptase (hTERT) is believed to be a rate-limiting step in telomerase activation. Recently, it has been proposed that the alternative splicing of hTERT is also involved in regulation of telomerase activity. However, the regulatory mechanism of telomerase in cancer cells has not been thoroughly investigated. To clarify it in lung cancer cells, we measured the expression of the hTERT transcript, analyzed its alternative splicing by RT-PCR, and compared it with telomerase activity and telomere length. The expression of the hTERT transcript was positively correlated with telomerase activity in lung cancer cells. Cancer cells with high telomerase activity contained 4 splicing variants of hTERT, and the full-length variant was 31.3-54.2% of the total transcripts. Cells of the TKB-20 cell line, which has extremely low telomerase activity, showed a different splicing pattern of hTERT in addition to low expression. The functional full-length variant was scarcely detected in TKB-20 cells, suggesting that the telomerase activity was repressed by alternative splicing of hTERT. Telomere length was not necessarily correlated with telomerase activity or hTERT expression in lung cancer cells. Cells of the TKB-4 cell line that also showed relatively low telomerase activity (as TKB-20 cells) had long telomeres. In conclusion, hTERT expression is regulated at both the transcriptional and post-transcriptional levels in lung cancer cells, and the alternative splicing of hTERT is involved in the control of telomerase activity.

Inflammatory pseudotumor-like follicular dendritic cell tumor of the spleen.

A case of so-called inflammatory pseudotumor (IPT), occurring in the spleen of a 77-year-old woman, is reported. The spleen contained a well-circumscribed mass with central hemorrhage and necrosis. Histologically, spindle cells were dispersed in a background of abundant inflammatory cells, predominantly lymphocytes and plasma cells. The cells possessed enlarged, sometimes twisted or irregularly folded, nuclei that contained vesicular chromatin, and small but distinct, centrally located nucleoli. Immunohistochemically, the spindle cells were diffusely positive for vimentin, and focally positive for follicular dendritic cell (FDC) markers (Ber-MAC-DRC for CD35 and CNA.42). The Epstein-Barr virus (EBV) was exclusively detected in the spindle cells by in situ hybridization analysis. The cells also expressed the latent membrane protein-1 (LMP-1) of EBV, and polymerase chain reaction (PCR) analysis revealed that the LMP-1 gene had a 30-bp deletion and three point mutations, although their significance remains controversial. Inflammatory pseudotumor is a descriptive term that encompasses several different entities, and recent investigations have revealed the existence of neoplastic entities among IPT. One of the neoplastic IPT, recently designated 'IPT-like FDC tumor', is characterized by proliferation of EBV-positive FDC and commonly occurs in the liver and spleen. Because such tumors are capable of recurrence and metastasis, it is important to consider the possibility of an IPT-like FDC tumor when making a diagnosis of a hepatic/splenic IPT-like lesion.

Angiomyofibroblastoma of the vulva: report of a case with immunohistochemical and molecular analysis.

A 43-year-old woman presented with a mass in the subcutaneous tissue of the right labium majus. A lipoma or Bartholin gland cyst was suspected and excision of the lesion was performed. The lesion was well circumscribed, and histological examination revealed a typical angiomyofibroblastoma. The lesion was composed of alternating hypocellular edematous and hypercellular areas with abundant vessels, and plump tumor cells were loosely dispersed or aggregated mainly around the vessels. Tumor cells were immunoreactive for vimentin and desmin but negative for muscle actins. Ultrastructurally, the tumor cells contained a moderate amount of rough endoplasmic reticulum and abundant intermediate filaments, and had primitive junctions. Pinocytotic vesicles or basal lamina were not evident. Immunohistochemical studies also revealed that the tumor cells expressed basic fibroblast-growth factor, vascular-endothelial-growth factor, and stem-cell factor, factors that may contribute to the rich vascularity and mast cells within the tumor. Reverse transcription-polymerase chain reaction detected high mobility group I-C (HMGI-C) transcripts in the tumor tissue. Because the expression of HMGI-C is regulated by developmental and differentiation processes and is not found in adult normal tissues, HMGI-C may be involved in the tumorigenesis of angiomyofibroblastoma.