Aim:　To　examine　whether　beta-adrenoceptor　(beta-AR)　agonists　can　induce　hypoxia-inducible　factor　(HIF)-1　alpha　accumulation　which　then　upregulate　the　expression　of　its　target　genes　in　pancreatic　cancer　cells　at　normoxia,　and　to　further　elucidate　the　mechanism　involved.　Methods:　Pulse-chase　assay,　RT-PCR,　and　Western　blot　were　employed　to　detect　the　effects　of　beta-AR　agonists　and　antagonists,　siRNA　as　well　as　several　inhibitors　of　signal　transduction　pathways　on　MIA　PaCa2　and　BxPC-3　pancreatic　cancer　cells.　Results:　Treatment　of　pancreatic　cancer　cell　lines　with　beta-AR　agonists　led　to　accumulation　of　HIF-1　alpha　and　then　up-regulated　expression　of　its　target　genes　independently　of　oxygen　levels.　The　induction　was　partly　or　completely　inhibited　not　only　by　beta-AR　antagonists　but　also　by　inhibitors　of　PKA　transduction　pathways　and　by　siHIF-1　alpha.　Both　beta　1-AR　and　beta　2-AR　agonists　produced　the　above-mentioned　effects,　but　beta　2-AR　agonist　was　more　potent.　Conclusion:　Activation　of　beta-AR　receptor　transactivates　epidermal　growth　factor　receptor　(EGFR)　and　then　elicites　Akt　and　ERK1/2　in　a　PKA-dependent　manner,　which　together　up-regulate　levels　of　HIF-1　alpha　and　downstream　target　genes　independently　of　oxygen　level.　Our　data　suggest　a　novel　mechanism　in　pancreatic　cancer　cells　that　links　beta-AR　and　HIF-1　alpha　signaling　under　normoxic　conditions,　with　implications　for　the　control　of　glucose　transport,　angiogenesis　and　metastasis.