Sperm protein 17 is a novel marker for predicting cisplatin response in esophageal squamous cancer cell lines.
Expression of sperm protein 17 (Sp17) mRNA has been reported in various malignancies. In an earlier study, we reported the upregulation of Sp17 transcripts in primary esophageal squamous cell carcinomas (ESCCs) using differential display and detected Sp17 transcripts in 86% of ESCCs by RT-PCR, whereas no transcripts were detected in the paired normal esophageal tissues. Herein we hypothesized that Sp17 might be used as a marker for detecting the response of anticancer therapies in ESCCs. Our results indicated that Sp17 protein levels in esophageal squamous cancer cell lines decreased in response to treatment with (i) the HSP90 activity inhibitor geldanamycin, (ii) the tyrosine kinase inhibitor erlotinib and (iii) cisplatin (chemotherapeutic agent commonly used in management of ESCC). In contrast, the Sp17 levels did not decrease in response to radiation therapy and treatment with the chemotherapeutic agent, gemcitabine. Further investigations showed that cisplatin induced decrease in Sp17 levels was due to transcriptional inhibition and cisplatin-resistant cell lines did not show this decrease in Sp17 levels in response to cisplatin treatment. In addition, we also carried our mass spectophotometric analysis to identify the binding partners of Sp17 to characterize its possible involvement in esophageal tumorigenesis and chemoresistance.
Kausar
Tasneem
T
Department of Biochemistry, All India Institute of Medical Science, New Delhi, India.
Ahsan
Aarif
A
Hasan
Md Raghibul
MR
Lin
Lin
L
Beer
David G
DG
Ralhan
Ranju
R
D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002148:Calmodulin-Binding Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D000069347:Erlotinib Hydrochloride; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D013058:Mass Spectrometry; D008565:Membrane Proteins; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011799:Quinazolines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects
D000954:Antigens, Surface; D000970:Antineoplastic Agents; D016227:Benzoquinones; D014408:Biomarkers, Tumor; D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D047029:Lactams, Macrocyclic; D008565:Membrane Proteins; D011799:Quinazolines; C090172:SPA17 protein, human; D000069347:Erlotinib Hydrochloride; D002945:Cisplatin; C001277:geldanamycin