title: Alterations associated with androgen receptor gene activation in salivary duct carcinoma of both sexes: potential therapeutic ramifications.
abstract: OBJECTIVE
  To investigate the molecular events associated with the activation of androgen receptor (AR) as a potential therapeutic target in patients with salivary duct carcinoma (SDC).
  
  
  METHODS
  Comprehensive molecular and expression analysis of the AR gene in 35 tumor specimens (20 males and 15 females) and cell lines derived from SDC using Western blotting and RT-PCR, FISH analysis, and DNA sequencing was conducted. In vitro and in vivo animal studies were also performed.
  
  
  RESULTS
  AR expression was detected in 70% of the tumors and was mainly nuclear and homogenous in both male and female SDCs, although variable cytoplasmic and/or nuclear localization was also found. We report the identification of ligand-independent AR splice variants, mutations, and extra AR gene copy in primary untreated SDC tumors. In contrast to prostate cancer, no AR gene amplification was observed. In vitro knockdown of AR in a female derived SDC cell line revealed marked growth inhibition in culture and in vivo androgen-independent tumor growth.
  
  
  CONCLUSIONS
  Our study provides new detailed information on the molecular and structural alterations associated with AR gene activation in SDC and sheds more light on the putative functional role of AR in SDC cells. On the basis of these data, we propose that patients with SDC (male and female) can be stratified for hormone-based therapy in future clinical trials.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Mitani
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Pulivarthi H
authors.initials: PH
authors.lastname: Rao
authors.affiliation: Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sankar N
authors.initials: SN
authors.lastname: Maity
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Renata
authors.initials: R
authors.lastname: Ferrarotto
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Julian C
authors.initials: JC
authors.lastname: Post
authors.affiliation: Head and Neck Cancer Medical Oncology Unit, Department of Medical Oncology, Fondazione IRCCS "Istituto Nazionale dei Tumori," Milan, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Licitra
authors.affiliation: Moores Cancer Center, University of California San Diego, San Diego, California.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Merrill S
authors.initials: MS
authors.lastname: Kies
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Randal S
authors.initials: RS
authors.lastname: Weber
authors.affiliation: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Carlos
authors.initials: C
authors.lastname: Caulin
authors.affiliation: Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sue-Hwa
authors.initials: SH
authors.lastname: Lin
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. anaggar@mdanderson.org.
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D000818:Animals; D044584:Carcinoma, Ductal / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D021381:Protein Transport; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D018987:Salivary Ducts / Q000473:pathology*; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D015533:Transcriptional Activation; D047368:Tumor Burden
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen