Down-regulation of transcription elogation factor A (SII) like 4 (TCEAL4) in anaplastic thyroid cancer

Abstract

Background: Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies and appears to arise mainly from transformation of pre-existing differentiated thyroid cancer (DTC). However, the carcinogenic mechanism of anaplastic transformation remains unclear. Previously, we investigated specific genes related to ATC based on gene expression profiling using cDNA microarray analysis. One of these genes, transcription elongation factor A (SII)-like 4 (TCEAL4), encodes a member of the transcription elongation factor A (SII)-like gene family. The detailed function of TCEAL4 has not been described nor has any association between this gene and human cancers been reported previously.

Methods: To investigate the role of TCEAL4 in ATC carcinogenesis, we examined expression levels of TCEAL4 in ACLs as well as in other types of thyroid cancers and normal human tissue.

Results: Expression of TCEAL4 was down-regulated in all 11 ACLs as compared to either normal thyroid tissues or papillary and follicular thyroid cancerous tissues. TCEAL4 was expressed ubiquitously in all normal human tissues tested.

Conclusion: To our knowledge, this is the first report of altered TCEAL4 expression in human cancers. We suggest that loss of TCEAL4 expression might be associated with development of ATC from DTC. Further functional studies are required.

Figure 1

(A) Decreased expression of TCEAL4 in ATCs as compared to normal thyroid tissues and PTCs as shown by SQ-PCR. The lane designations are as follows: M, size markers; 1–5, normal thyroid samples, 6–10, primary papillary thyroid cancer samples, 11–15, primary anaplastic thyroid cancer samples. (B) Results of quantitative RT-PCR. The average expression level of TCEAL4 among five normal thyroid tissues was set at 1.00, then relative expression ratios were calculated between normal and cancerous tissues.

Figure 2

(A) Down-regulation of TCEAL4 in ACLs as compared to normal thyroid tissues as shown by SQ-PCR. The following are the lane designations: M, size marker; 1–5, normal thyroid; 6, 8305c; 7, 8505c; 8, ARO; 9, FRO; 10, TTA1; 11, TTA2; 12, TTA3; 13, KTA1; 14, KTA2; 15, KTA3; 16, KTA4. (B) Results of quantitative RT-PCR. TCEAL4 expression of normal thyroid is the average of five normal thyroid glands. When the expression of normal thyroid was settled as 1.00, the ratio represented relative expression of TCEAL4 in the sample.

Figure 3

SQ-PCR analysis of the expression of TCEAL4 in 91 of cancer cell lines. The lanes are designated as: M, size marker; 1, SK-HEP-1; 2, Hep G2; 3, C-HC-4; 4, Hep-KANO CL2; 5, Hep-TABATA; 6, HuH7; 7, HT17; 8, Li-7; 9, PLC/PRF/5; 10, Hep38; 11, WRL68; 12, Chang Liver; 13, C3A; 14, HuGC-OOHIRA; 15, AZ521; 16, H-111-TC; 17, SH-10-TC; 18, MKN-7; 19, NUGC-4; 20, DLD-1; 21, SW480; 22, HCT-15; 23, WiDr; 24, MIA Paca2; 25, PK8; 26, MDA-MB-453; 27, CDL1500; 28, YMB-1-E; 29, MCF7; 30, HBL100; 31, WRO; 32, NPA; 33, ARO; 34, FRO; 35, 8505c; 36, 8305c; 37, CAOV-3; 38, SK-OV-3; 39, OVCAR-3; 40, OV-1063; 41, OVK18; 42, SIHA; 43, HT-3; 44, D98-AH2; 45, Hela TG; 46, Hela; 47, Ca Ski; 48, Me-180; 49, Hela.P3; 50, RERF-LC AI; 51, PC-14; 52, A549; 53, EBC-1; 54, LU65; 55, LU99; 56, LK-2; 57, 5637; 58, T24; 59, EJ-1; 60, OS-RC-2; 61, RCC10RGB; 62, VMRC-RCW; 63, Caki-1; 64, HuH-28; 65, TFK-1; 66, MG-63; 67, Saos02; 68, HuO-3N1; 69, U-2OS; 70, IMR-32; 71, NH-12; 72, SCCH-26; 73, NB-1; 74, TE671; 75, U-138MG; 76, U-373MG; 77, U-118MG; 78, KG-1-C; 79, GI-1; 80, U251; 81, SW1088; 82, Daoy; 83, DBTRG-05MG; 84, D283 Med; 85, A172; 86, T98G; 87, u87MG; 88, u251MG; 89, SNB19; 90, uw18; 91, uw228.

Figure 4

Expression of TCEAL4 in normal human tissues. The following are the lane designations: M, size marker; 1, heart; 2, brain; 3, placenta; 4, lung; 5, liver; 6, skeletal muscle; 7, kidney; 8, spleen; 9, pancreas; 10, thymus; 11, prostate; 12, testis; 13, ovary; 14, small intestine; 15, colon; 16, leukocytes; 17, thyroid.