Expression of a truncated form of hHb1 hair keratin in human breast carcinomas

Régnier, Catherine H.; Boulay, Anne; Asch, P H; Wendling, Corinne; Chenard, Marie–Pierre; Tomasetto, Catherine; Rio, Marie‐Christine

doi:10.1038/bjc.1998.736

Cited by 13 publications

(17 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surprisingly, although the normal hHb1 promoter is silent in normal and malignant breast cells, because no full-length hHb1 mRNA was detected in these cells, a truncated hHb1 mRNA isoform (hHb1-⌬N) was observed in cancerous epithelial cells of breast carcinomas (4,5). Thus, hHb1 is the first hair keratin whose expression was documented in carcinomas other than skin carcinomas.…”

Section: Discussionmentioning

confidence: 98%

“…MLN137 was therefore called hHb1-⌬N, because the putative protein corresponded to an hHb1 keratin truncated at its amino terminus. In situ hybridization showed that the hHb1-⌬N mRNA is ectopically expressed in malignant epithelial cells of primary breast carcinomas and metastases (5). This truncated transcript has thus far never been detected in hairy skin samples.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Transcription Regulation and Protein Subcellular Localization of the Truncated Basic Hair Keratin hHb1-ΔN in Human Breast Cancer Cells

Boulay¹,

Régnier

Anglard

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

An aberrant truncated hHb1 hair keratin transcript, named hHb1-⌬N, was previously identified in breast carcinomas. No normal tissue tested so far, including hairy skin, expressed hHb1-⌬N, indicating that hHb1-⌬N is related to carcinogenesis. In the present study, we investigated the mechanism by which such truncated transcript was generated in breast cancer cell lines. We found that hHb1-⌬N transcription is initiated at an unusual cryptic promoter within the fourth intron of the hHb1 gene and is dependent on two proximal Sp1 binding sites for its baseline activity. Moreover, hHb1-⌬N transcription is increased in response to DNA demethylation by the 5-aza-2-deoxycytidine drug. This induction is dependent on protein neosynthesis, indicating that an additional factor is required. In addition, we showed that the hHb1-⌬N transcript is translated in vivo as a truncated hHb1 protein that is missing the 270 amino-terminal residues. The hHb1-⌬N protein exhibits a filament pattern throughout the cytoplasm and partially co-localizes with cytokeratin filaments, indicating its participation in the cytoskeleton network. hHb1-⌬N might alter the adhesive properties of cancer cells.

show abstract

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Transcription Regulation and Protein Subcellular Localization of the Truncated Basic Hair Keratin hHb1-ΔN in Human Breast Cancer Cells

Boulay¹,

Régnier

Anglard

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated that hHb1 is abundantly expressed in the di erentiating cortex of growing hair (Bowden et al, 1998). Additionally, Regnier et al (1998) have demonstrated that a truncated version of the hHb1 gene, which is missing about 800 base pairs of DNA at the 5' end, is expressed in human breast carcinomas. We have found both full length and truncated forms of hHb1 gene in breast tumors.…”

Section: Identification Of Cdnas Differentially Expressed In Breast Tmentioning

confidence: 99%

Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays

et al. 2002

View full text Add to dashboard Cite

Identifying novel and known genes that are di erentially expressed in breast cancer has important implications in understanding the biology of breast tumorigenesis and developing new diagnostic and therapeutic agents. In this study we have combined two powerful technologies, PCRbased cDNA subtraction and cDNA microarray, as a high throughput methodology designed to identify cDNA clones that are breast tumor-and tissue-speci®c and are overexpressed in breast tumors. Approximately 2000 cDNA clones generated from the subtracted breast tumor library were arrayed on the microarray chips. The arrayed target cDNAs were then hybridized with 30 pairs of¯uorescent-labeled cDNA probes generated from breast tumors and normal tissues to determine the tissue distribution and tumor speci®city. cDNA clones showing overexpression in breast tumors by microarray were further analysed by DNA sequencing, GenBank and EST database searches, and quantitative real time PCR. We identi®ed several known genes, including mammaglobin, cytokeratin 19, ®bronectin, and hair-speci®c type II keratin, which have previously been shown to be overexpressed in breast tumors and may play an important role in the malignance of breast. We also discovered B726P which appears to be an isoform of NY-BR-1, a breast tissue-speci®c gene. Two additional clones discovered, B709P and GABA A receptor p subunit, were not previously described for their overexpression pro®le in breast tumors. Thus, combining PCRbased cDNA subtraction and cDNA microarray allowed for an e cient way to identify and validate genes with elevated mRNA expression levels in breast cancer that may potentially be involved in breast cancer progression. These di erentially expressed genes may be of potential utility as therapeutic and diagnostic targets for breast cancer.

show abstract

“…35 S-Labeled cRNA transcripts of hKAP1.5, hKAP2.4, hKAP3.3, hKAP4.3, and hKAP9.2 derived from subcloned 3Ј-noncoding region PCR probes (see Table I) were used for detection of the respective KAP mRNA species. Specific ISH signals were visualized using a confocal laser scanning microscope (LSM 510; Carl Zeiss, Jena, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…Hair Follicle KAP Expression-Radioactive in situ hybridizations using 35 S-labeled 3Ј-noncoding region probes derived from representative members of each multigene KAP family found on the DNA contig (hKAP1.5, hKAP2.4, hKAP3.3, hKAP4.3, and hKAP9.2) were performed on cryosections of human scalp epidermis (a detailed expression study of all KAP members is in progress). 2 Four of the probes were specific for each of the respective genes analyzed (hKAP1.5, hKAP2.4, hKAP3.3, and hKAP4.3).…”

Section: Carboxyl-terminal Amino Acid Sequences (Amino Terminus Mt(hmentioning

confidence: 99%

Characterization of a Cluster of Human High/Ultrahigh Sulfur Keratin-associated Protein Genes Embedded in the Type I Keratin Gene Domain on Chromosome 17q12-21

Rogers¹,

Langbein²,

Winter³

et al. 2001

Journal of Biological Chemistry

149

View full text Add to dashboard Cite

Low stringency screening of a human P1 artificial chromosome library using a human hair keratin-associated protein (hKAP1.1A) gene probe resulted in the isolation of six P1 artificial chromosome clones. End sequencing and EMBO/GenBank TM data base analysis showed these clones to be contained in four previously sequenced human bacterial artificial chromosome clones present on chromosome 17q12-21 and arrayed into two large contigs of 290 and 225 kilobase pairs (kb) in size. A fifth, partially sequenced human bacterial artificial chromosome clone data base sequence overlapped and closed both of these contigs. One end of this 600-kb cluster harbored six gene loci for previously described human type I hair keratin genes. The other end of this cluster contained the human type I cytokeratin K20 and K12 gene loci. The center of the cluster, starting 35 kb downstream of the hHa3-I hair keratin gene, contained 37 genes for high/ultrahigh sulfur hair keratinassociated proteins (KAPs), which could be divided into a total of 7 KAP multigene families based on amino acid homology comparisons with previously identified sheep, mouse, and rabbit KAPs. To date, 26 human KAP cDNA clones have been isolated through screening of an arrayed human scalp cDNA library by means of specific 3-noncoding region polymerase chain reaction probes derived from the identified KAP gene sequences. This screening also yielded four additional cDNA sequences whose genes were not present on this gene cluster but belonged to specific KAP gene families present on this contig. Hair follicle in situ hybridization data for single members of five different KAP multigene families all showed localization of the respective mRNAs to the upper cortex of the hair shaft.

show abstract

Expression of a truncated form of hHb1 hair keratin in human breast carcinomas

Cited by 13 publications

References 18 publications

Transcription Regulation and Protein Subcellular Localization of the Truncated Basic Hair Keratin hHb1-ΔN in Human Breast Cancer Cells

Transcription Regulation and Protein Subcellular Localization of the Truncated Basic Hair Keratin hHb1-ΔN in Human Breast Cancer Cells

Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays

Characterization of a Cluster of Human High/Ultrahigh Sulfur Keratin-associated Protein Genes Embedded in the Type I Keratin Gene Domain on Chromosome 17q12-21

Contact Info

Product

Resources

About